Search tips
Search criteria 


Logo of cdiJournal's HomeManuscript SubmissionAims and ScopeAuthor GuidelinesEditorial BoardHome
Clin Dev Immunol. 2011; 2011: 790460.
Published online 2011 March 22. doi:  10.1155/2011/790460
PMCID: PMC3095450

Exogenous Control of the Expression of Group I CD1 Molecules Competent for Presentation of Microbial Nonpeptide Antigens to Human T Lymphocytes


Group I CD1 (CD1a, CD1b, and CD1c) glycoproteins expressed on immature and mature dendritic cells present nonpeptide antigens (i.e., lipid or glycolipid molecules mainly of microbial origin) to T cells. Cytotoxic CD1-restricted T lymphocytes recognizing mycobacterial lipid antigens were found in tuberculosis patients. However, thanks to a complex interplay between mycobacteria and CD1 system, M. tuberculosis possesses a successful tactic based, at least in part, on CD1 downregulation to evade CD1-dependent immunity. On the ground of these findings, it is reasonable to hypothesize that modulation of CD1 protein expression by chemical, biological, or infectious agents could influence host's immune reactivity against M. tuberculosis-associated lipids, possibly affecting antitubercular resistance. This scenario prompted us to perform a detailed analysis of the literature concerning the effect of external agents on Group I CD1 expression in order to obtain valuable information on the possible strategies to be adopted for driving properly CD1-dependent immune functions in human pathology and in particular, in human tuberculosis.

1. Introduction

Cell-mediated immunity involved in host resistance against mycobacteria and other infectious agents appears to rely to a large extent on classical HLA-restricted responses against microbial peptides [1] mediated mainly by interferon (IFN) γ-producing T-cells [2]. However, in recent years growing attention has been given to T-cell-mediated responses directed against lipid or glycolipid antigens presented by four relatively nonpolymorphic CD1molecules ([35], reviewed in [6]).

Two groups of CD1 isoforms expressed on the cell membrane of various antigen-presenting cells (APCs) have been identified in the course of the last 20 years. In particular, Group I (i.e., CD1a, CD1b, CD1c) and the isoform CD1e, that is confined to the intracellular compartment and is classified as Group III by some authors, are detectable in man but not in mice. On the contrary, Group II (i.e., CD1d, a biological entity outside the scope of the present review) is expressed in mice and men as well, and is involved in Invariant Natural Killer T-cell responses (specifically reviewed in [7]). The molecular structure of CD1 is similar to that of MHC class I. Both CD1 and MHC class I are comprised of heavy chains of similar length, which are organized into three extracellular domains (α1, α2, and α3) and bind β2 microglobulin.

Group I CD1 molecules are expressed most prominently on APCs of the myeloid lineage, including dendritic cells (DCs) derived from circulating monocytes (MOs). Peripheral blood CD1/CD14+ MOs can be activated by granulocyte-macrophage colony stimulating factor (GM-CSF) alone or more efficiently in combination with interleukin-4 (IL-4) (i.e., GM-CSF + IL-4, hereafter referred to as G4) to express Group I CD1 glycoproteins [9, 10]. These molecules are the products of the CD1A, -B, and -C genes and are known to be involved in the presentation of nonpeptide microbial antigens to T-cells [6, 1012]. In particular, Beckman et al. in 1994 [13] discovered that the CD1b-presented antigens obtained from Mycobacterium tuberculosis were mycolic acids, that is, lipids associated with microbial cell wall. Later, it was demonstrated that CD1 molecules are competent for presentation of a great variety of microbial antigenic lipid structures to T-cells, so that CD1 could be tentatively considered a wide spectrum system of anti-infectious immune surveillance [6].

Particular attention of the present review is dedicated to the studies concerning the CD1 system predominantly engaged in antitubercular responses, and therefore involved in mycobacterial lipid presentation to CD1-restricted T-cells. A fraction of responder T-cells comes from the CD4/CD8 phenotypic subset of CD3+ T-cell receptor (TCR) α/β T-cells. These cells, sometimes referred to as double-negative TCR α/β T lymphocytes [14], proliferate and generate cytotoxic clones following interaction with mycobacterial glycolipids, presented by CD1b+ DCs-derived from G4-preactivated MOs. However, CD1-restricted CD8+ or CD4+TCR α/β T-cell clones [15, 16] and TCR γ/δ T-cells [3, 17] have also been demonstrated. Thus, responder cells that potentially play a role in CD1-restricted responses to nonpeptide antigens, have been found to belong to all of the major phenotypic subsets of T-cells. Noteworthy is the general observation that CD1-restricted recognition of bacteria-associated lipids results in killing of the infected cells as well as of the microorganism, thus providing presumably a way to prevent infection spreading in the host [15, 18].

The induction of effector T-cells against microbial antigens is accompanied by the presence of autoreactive CD1-restricted T-cells directed against self-lipid antigens [19]. These lymphocytes appear to cooperate in early suppression of invading microorganisms, in the induction of CD1-restricted memory T-cells and in the maturation of DCs able to produce substantial amounts of IL-12. In turn, IL-12 stimulates T-cells to produce IFNγ (reviewed in [20]) and plays an important role in antitubercular immunity [21]. Autoreactive CD1-restricted T-cells have also been accused to take part in the immune mechanisms underlying multiple sclerosis (MS) and Guillan-Barre syndrome [22, 23]. However, detection of autoreactive cytotoxic T lymphocytes in patients affected by autoimmune disease, does not necessarily mean that these cells play a role in the pathological events affecting target organs.

Up to now, it has not been definitely established whether tuberculosis prevention could be achieved through vaccinial procedures based on M. tuberculosis-associated lipids as sensitizing agents. Improvement in the course of the disease has been noted in guinea pigs sensitized with lipid extracts of M. tuberculosis [24, 25]. Moreover, a recent study published by Felio et al. [26] showed that human Group I CD1 transgenic mice are competent for mounting a CD1-restricted adaptive immune responses to mycobacteria, thus allowing further preclinical investigations on lipid-based antitubercular vaccines in mouse models.

In view of a potential role of Group I CD1 glycoprotein-dependent presentation of mycobacterial lipids to T-cells, it is reasonable to hypothesize that pharmacological or biological agents able to modulate CD1 expression could modify host's responses against infectious diseases, including infections caused by M. tuberculosis. Therefore, the aim of the present short survey is to illustrate the data presently available in the literature, relative to the influence that can be exerted by external agents on Group I CD1 molecule expression. In particular, the reported studies will consider human MOs driven in vitro or in vivo to differentiate into immature and thereafter mature DCs (Figures (Figures11 and and2)2) competent for peptide or nonpeptide molecule presentation to T-cells.

Figure 1
Dendritic Cell (DC) generation and maturation. Schematic drawing depicting the differentiation of monocytes to immature DC (iDC), generation of mature DC (mDC) and cytokines involved in these processes. Dotted lines point to the modulating effects ...
Figure 2
Effect of external agents on group I CD1 glycoprotein expression.

2. In Vitro and In Vivo Assays of CD1 Induction

A classical experimental design to explore the functional pathways involved in the differentiation and maturation of human myeloid DCs in vitro system, starting from purified CD14+ MOs obtained from peripheral blood mononuclear cells (PBMNC), can be described as follows (Figure 2):

Step 1 —

In vitro cultivation of MOs with G4 for 3–6 days (or, in some cases, for up to 7 days). This treatment is able to induce “immature DCs” (iDCs) showing high expression of CD1a, CD1b, and CD1c glycoproteins on cell membrane, competent for lipid antigen presentation to CD1-restricted T-cells.

Step 2 —

In vitro culture of iDCs with lipopolysaccharide (LPS) and/or various cytokines (e.g., TNFα, IFNα, TGFβ, etc.) for additional 2-3 days, leading to mature CD83+ DCs (mDCs), fully competent to behave as classical APCs.

In a large number of studies published in more than 15 years, iDCs have been also generated from cord blood CD34+ cells cultured in vitro with a cocktail of cytokines containing GM-CSF. In addition, several investigations have been conducted in vivo by evaluating the number of DCs in various organs, in different clinical and treatment conditions using immunohistochemical detection of mainly CD1a+ cells.

All these methods, able to explore the functional pathways leading to mDCs, allowed to test the effect of a number of exogenous agents on the expression of Group I CD1 molecules induced in host's cell population involved in resistance against pathogens, including mycobacteria.

In order to offer a concise picture on the external control of CD1 expression, the present review provides information on the complex relationship between mycobacteria and CD1 levels, and four tables summarize schematically what we presently know on the regulation of CD1 expression by pharmacological and biological agents. Moreover, with the intent to provide a simplified information on the experimental strategy utilized for studying the influence exerted by exogenous agents on CD1 expression during myeloid DCs induction and maturation, we decided to adopt the codes that are illustrated in Figure 2.

3. CD1 Expression

It is generally agreed that transcriptional control of gene expression and posttranscriptional regulation of mRNA function are usually under the control of proteins targeting specific DNA sequences (i.e., transcription factors) and microRNAs, respectively. In particular, expression of Group I CD1 genes is under the control of transcription factors, that have been described in detail for CD1a glycoprotein by Colmone et al. [27]. A minimal 1000-bp region upstream of the translation start site has been identified as necessary for proximal promoter activity required for CD1A transcription. This region contains multiple sites that were considered to be coordinatively involved in CD1A gene expression on the basis of a series of experiments performed by means of deletion and site-specific mutant analysis. In particular, a critical role appeared to be played by a potential cAMP response element (CRE), 965 bp upstream of the CD1A translation start site. It was found that the CRE-binding protein 1 (CREB-1) and the activating transcription factors-2 (ATF-2) that are enlisted among the ATF/CREB family members, are able to bind this site in vitro and in vivo in various cell types, including human MOs [27]. Moreover, the results of these studies speak in favour of ATF-2-induced inhibition counterbalanced by a stimulatory activity on gene transcription by CREB-1, possibly through a competition of CREB-1 and ATF-2 for CRE binding. The hypothesis of opposite control performed by two transcription factors acting on the same gene promoter appears to be supported by the studies published by Niwano et al. [28] who proposed a similar mechanism for endothelial nitric oxide synthase.

In the present survey of the literature, we noticed the emerging role played by miRNAs on hematopoiesis (reviewed in [29]). Therefore, we have considered the possibility that miRNAs could affect CD1 expression. An in silico analysis was performed using the miRanda ( and TargetScan ( algorithms for miRNA target prediction. Under miRanda analysis, miRNA list indicates conserved miRNAs with good mirSVR scores [8]. As illustrated in Table 1, this analysis revealed that mRNAs transcribed from all three Group I CD1 genes can be targeted and potentially regulated at the 3′UTR region by a number of different miRNAs. In particular, 10 miRNAs have been found to share a potential capability of controlling the transcriptional activity of two CD1 genes. Six miRNAs (i.e., 33a, 33b, 421, 495, 590-3p, and 590-5p) could target both CD1a and CD1c, whereas miRNA-224 could be active on CD1a and CD1b, and 3 miRNAs (i.e., 129-5p, 185 and 203) appear to be theoretically competent to target CD1b and CD1c. However, up to now no study able to validate the in silico prediction patterns is available from the literature. Nevertheless, a number of miR genes have been found to be involved in the regulation of immune responses [30, 31] and acute inflammation [32]. Moreover, quite recently Kuipers et al. [33] described that microRNAs control maturation, function, and maintenance of DCs in the epidermis (i.e., Langerhans cells, LC) in vivo. In addition, exchange of genetic material between prokaryotic and eukaryotic multicellular organisms has been described [34]. Therefore, since pathogenic microorganisms, including mycobacteria contain a large amount of small noncoding RNA [35, 36], it is reasonable to hypothesize that invading microbes could control gene expression of host eukaryotic cell through their miRNA-like molecules to acquire a survival advantage.

Table 1
miRNAs with putative binding sites in the 3′UTR of CD1A, CD1B, and CD1C genes.

4. Mycobacteria and CD1 Expression

Anti-tubercular immunity relies on humoral and cell-mediated immune responses against M. tuberculosis-associated epitopes of various origin, and possibly includes CD1-presented lipid antigens recognized by dedicated T-cell subpopulations [37]. More than eighty years ago, attenuated strains of M. bovis (i.e., Bacillus Calmette-Guerin, BCG) were developed and utilized as antitubercular vaccine, since they share a variety of antigenic molecules with virulent pathogenic bacilli [38]. Although BCG vaccine reduces the risk of severe forms of tuberculosis in early childhood, unfortunately it is not very effective in preventing the pulmonary infection in adolescents and adults, the populations with the highest rates of tuberculosis disease. Moreover, M. tuberculosis is changing and evolving, making the development of new vaccines [39] more crucial to control the disease that is continuously expanding, favored, at least in part, by AIDS pandemia.

In the last years, a considerable amount of experimental studies has been dedicated to investigate the complex relationship between the infection with virulent M. tuberculosis or BCG and functional activity of the CD1 system. A number of studies confirm that lipid antigens recognized and presented by Group I CD1 glycoproteins include fatty acids isolated from M. tuberculosis cell wall [40]. Among others, they comprise the fatty-acid-derived mycolic acid, the lipopeptide didehydroxymycobactin [41], the isoprenoid-like structure mannosyl phosphomycoketide [42], and the acylated sulfoglycolipid Ac2SGL [43].

In this context, CD1b appears to play a particularly important role, since CD1b-restricted T lymphocytes recognize a large variety of mycobacterial lipids [44], including M. tuberculosis Ac2SGL antigens [45]. Moreover, CD1b groove is much larger than that associated with the other CD1 isoforms, so that it can adjust long chain foreign lipids, including long mycobacterial mycolates that are not presented by the other CD1 molecules [46]. On the basis of all these findings and taking into account additional information from the literature (reviewed in [6, 46]), it is reasonable to consider Group I CD1 as a relevant part of the complex antigen-presenting systems involved in the T-cell-dependent immune response machinery against mycobacteria. Actually, in human leprosy lesions CD1 expression correlates with host immunity as manifested by active cellular immunity to M. leprae [47]. A number of clinical and experimental data indicate that long-lived immunity to M. tuberculosis relies largely on antigen-specific CD4+ and CD8+ T-cells that could play consistent roles in vaccination strategies [48]. Therefore it is reasonable to hypothesize that CD1-restricted effector T lymphocytes, that show a limited repertoire but are able to recognize large amounts of lipid antigens based on antigenic cross-reactivity [49], would contribute to antitubercular immunity. Ulrichs et al. [50] collected PBMNC from patients with pulmonary tuberculosis, from asymptomatic individuals with known contact with M. tuberculosis documented by conversion of their tuberculin skin tests, and from healthy tuberculin skin test negative subjects. In vitro, in presence of autologous CD1+ iDCs, the extent of CD1-restricted T-cell responses to a lipid extract of M. tuberculosis was tested by means of proliferation and IFNγ production by effector T-cells. The results showed that T-cells from asymptomatic M. tuberculosis-infected donors were significantly more responsive than those obtained from uninfected healthy donors. Moreover, essentially no CD1-restricted T-cell response was detectable in lymphocytes collected from patients with active tuberculosis prior to chemotherapy. However, significant antilipid immune reactivity became detectable in blood samples drawn two weeks after the start of treatment, as a possible consequence of chemotherapy-induced relief of the inhibitory effect exerted by mycobacteria on cell-mediated immunity [51].

In order to better define the possible role that can be played by CD1-dependent antimycobacterial immunity, it is important to identify the target of CD1-restricted effector T-cells and the modality of target suppression. Of note are the findings illustrated by Vincent et al. [52] who used CD1-restricted human α/β T-cells generated by autologous DCs in presence of microbial detergent extracts from M. tuberculosis, E. coli, or Y. enterocolitica. Effector T-cells were found to be active in terms of proliferation and IFNγ release when tested against target cells presenting microbial lipid antigens via CD1a, CD1b, or CD1c molecules. However, similar activity, although to a lower extent, was detected in absence of foreign lipids, thus indicating that sensitized lymphocytes were also endowed with effector function against self-lipids. The authors propose that CD1-restricted T lymphocytes fit in two T-cell populations, that is, naive T lymphocytes able to mount an adaptive response to microbial lipids as well as memory/effector T-cells. The latter population, characterized by reactivity against self and foreign lipids, would be particularly dedicated to rapid initial immune responses against invading pathogens and yet able to undergo clonal expansion responsible for long-standing cellular memory to foreign lipid antigens. Actually, Nguyen et al. [53] have recently reported that upon experimental vaccination of cattle, CD1b-restricted memory T-cell response can be elicited by the mycobacterial glycolipid glucose monomycolate.

The effector function of T lymphocytes against microbial targets, including M. tuberculosis follows a rather complex pattern (reviewed in [20]). When primed T-cells interact with CD1+ mycobacteria-infected target cells, they kill directly mycobacteria through granulysin/perforin-based mechanism release [54], or they induce Fas-dependent apoptotic death of target cells without killing the intracellular infectious agent. In this case mycobacteria are released and infect adjacent macrophages and DCs where invading bacilli are possibly killed, depending on microbial burden. In addition to direct cytotoxic effects, CD1-restricted T-lymphocytes release Th1 cytokines (i.e., IFNγ and TNFα) that activate the microbicidal functions of macrophages and DCs [20].

Recently, the role of IFNγ released by CD1-restricted effector T-cells has been subjected to detailed analysis by Lee and Kornfeld [55]. These authors reported that IFNγ released by T-cells inhibits bacterial replication in infected macrophages carrying low intracellular burden of mycobacteria, thus contributing to host defenses against tuberculosis. However, when macrophages are engulfed with high bacteria load, IFNγ facilitates host cell death, thus promoting necrosis and spreading of the infection, with potentially adverse effects on the course of the disease.

A large body of experimental data is presently available from the literature showing that mycobacteria have developed highly sophisticated strategies to escape host's resistance based either on innate or adaptive immunity (reviewed in [56]). Tuberculosis is predominantly a lung disease characterized by long chronic course due to persistent and sometimes dormant infection. It is well documented that upon contact with inhaled M. tuberculosis, both alveolar macrophages, that do not express CD1 molecules, and CD1+ DCs phagocytose mycobacteria. But most of the microorganisms are taken up by macrophages that are by far more efficient than resident lung DCs in the ability to phagocytose and possibly kill bacteria [57]. However, the fate of M. tuberculosis within the infected alveolar macrophage depends on the state of activation of the phagocyte. Actually, the bacillus is able to survive preferentially within a macrophage subpopulation displaying an anti-inflammatory phenotype with a reduced oxidative burst. Moreover, phagocytosed mycobacteria end up in a phagosome, the maturation of which is arrested at an early stage [58], at least in part by mycobacteria-released glycolipids, such as lipoarabinomannan and phosphatidylinositol mannoside [59]. M. tuberculosis inhibits phagosomal acidification, prevents phagosome-lysosome fusion and survives within macrophages by avoiding lysosomal delivery thanks, at least in part, to coronin 1 that is actively recruited to mycobacterial phagosomes [60]. Since alveolar macrophages do not express CD1 molecules, and mycobacterial peptide antigens confined to phagosomes are excluded from the classical MHC-I presentation pathway, they cannot be targeted by MHC-I- or CD1-restricted cytotoxic lymphocytes. Therefore, in the lung environment, host's defenses against mycobacteria are mainly activated through apoptosis induction of infected alveolar macrophages followed by cross-priming of resident DCs endowed with the appropriate machinery for peptide and lipid/glycolipid antigen presentation to T-cells [61]. However, mycobacterial infection inhibits specifically macrophage apoptosis [62], thus preventing DC cross-priming and consequently providing an additional mechanism of impairment of host's T-cell defenses based on bacterial antigen recognition.

Infection with M. tuberculosis can also adversely affect DC function by interfering with their expression pattern of antigen-presenting molecules. Therefore, among the different escape mechanisms operated by mycobacteria, of particular relevance for the present survey are the complex autocrine and paracrine devices that the microorganism uses to control the induction of Group I CD1 molecule expression in infected and adjacent noninfected MOs. In 1998 Stenger et al. [63] exposed in vitro MOs from healthy donors to G4 for 3 days, obtaining iDCs expressing high levels of Group I CD1 glycoproteins. Thereafter, iDCs were heavily infected with M. tuberculosis that was able to suppress entirely CD1 expression within 24 h independently from any cytokine intervention. On the other hand, Prete et al. [64] reported later that in vitro coculture of BCG with untreated MOs was able to induce GM-CSF release by infected cells leading to limited CD1b expression. Modest upregulation of Group I CD1 antigen expression was also described by Roura-Mir et al. [65] in untreated MOs after in vitro infection with M. tuberculosis at 2 or 10 bacteria per cell. These authors report that their findings could be explained, at least in part, through Toll-like receptor-2 (TLR-2) signaling induced by mycobacterial cell wall lipids. A possible, although limited induction of CD1 expression by mycobacteria has also been described in vivo. Videira et al. [66] found that prophylactic administration of intravesical BCG to prevent tumor recurrence in bladder cancer patients, was followed by upregulation of CD1A, CD1B, CD1C, and CD1E gene transcripts in cells obtained from urothelium biopsies. This effect was significantly higher in patients with a more favorable response with respect to that observed in patients with early tumour recurrence [66]. Marked accumulation of CD1a+ LC after mycobacterial stimuli was also described in leprosy skin lesions [67]. On the other hand, in vitro maturation of MOs to CD1a+ DCs under the influence of G4 and LPS was found to be sensibly impaired when MOs were collected from patients with pulmonary tuberculosis [68]. The intriguing Janus-like behavior of mycobacteria relative to CD1 expression has been investigated in 2001 by Prete et al. [69] and Giuliani et al. [70], who found that BCG induced in vitro a limited expression of CD1 in untreated MOs from healthy donors, but inhibited markedly G4-induced CD1 upregulation in the same cells. Thereafter, further investigations confirmed that in vitro infection with mycobacteria downregulates CD1 expression [71, 72]. In particular, upon exposure to G4, MOs infected with M. smegmatis failed to express CD1a and evolved directly into CD83+ mDCs [73]. In 2007, Prete et al. [74] provided direct experimental evidence that in vitro exposure of healthy MOs to BCG induced release of both GM-CSF and IL-10, and that the interplay between the two cytokines was presumably involved, at least in part, in the Janus-like behavior of BCG. Actually, early GM-CSF release was responsible for the limited autocrine and paracrine CD1 induction. On the other hand, slightly delayed appearance in culture medium of IL-10 produced by BCG-infected MOs contributed to the severe limitation of further increase of CD1 proteins, even in the presence of exceedingly high concentrations of added GM-CSF. More recently, Gagliardi et al. [75] reported that mycobacteria trigger phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in human MOs, leading to CD1 expression impairment. In fact, pretreatment with a specific p38 MAPK inhibitor allows infected MOs to differentiate into CD1+ DCs, which are fully capable of presenting lipid antigens to specific T-cells. Further studies have been conducted on the possible role of cytokines in restraining the GM-CSF-induced upregulation of Group I CD1 glycoproteins in mycobacteria infected MOs. Quite recently, Remoli et al. [76] confirmed the results of the studies described by Prete et al. [74] showing that IL-10 produced by MOs infected with M. tuberculosis is responsible for in vitro suppression of CD1. Moreover, consistently with the results obtained previously by the same group [75], they suggested that IL-10 release by infected MOs was induced by the activation of p38 MAPK signal transduction pathways. Several reports from the literature indicate that mycobacteria activate IL-10 gene and promote IL-10 release from MOs, phagocytes, and DCs through different intracellular pathways, including PI3K/AKT and p38 MAPK [7781], phosphorylation and activation of dsRNA-activated serine/threonine protein kinase [82] and glycogen synthase kinase 3 [83]. Noteworthy is the role of proline-glutamic acid/proline-proline-glutamic acid family of proteins of M. tuberculosis that can stimulate macrophages to secrete IL-10 via activation of the TLR-2 leading to an early and sustained activation of p38 MAPK, which is critical for IL-10 induction [84]. The role of MAPK in the impairment of CD1 expression by mycobacteria has been also confirmed and emphasized very recently by Balboa et al. [85] who found that mycobacteria-induced loss of CD1b molecules partially involves TLR-2/p38MAPK activation.

Several other molecular mechanisms distinct from those relative to impairment of CD1 gene transcription could be involved in mycobacteria-induced decrease of CD1 expression or of antigen presentation efficiency. The complex cycle of CD1 biosynthesis, cell surface expression, and lipid loading [12, 44, 86] highlights the several means by which mycobacteria can interfere with CD1 expression on cell membrane and antigen presentation to T-cells. After biosynthesis in the endoplasmic reticulum, CD1e remains in the cell, whereas all other CD1 molecules reach the cell surface through the Golgi and trans-Golgi network where they bind to self-lipids. Direct loading of lipids may occur at the plasma membrane, as described for glycosphingolipids that bind to CD1b on the cell surface at neutral pH. Thereafter, glycosphingolipids are recognized without internalization or processing and stimulate specific T-cells [87]. Moreover, various cell-surface CD1a proteins are stabilized by exogenous glycosphingolipids and phospholipids present in serum [88].

As a rule, processing and presentation of microbial CD1-bound lipid antigens require that CD1 molecules, loaded with self-lipids, undergo a recycle process. CD1-self lipid complexes are internalized, traffic through the endosomal compartments, where loading and/or exchange with exogenous lipid antigens occur, then the new CD1-nonself lipid complexes re-emerge on plasma membrane. This process resembles peptide sampling by MHC class II proteins, although MHC class II molecules may reach the endocytic compartment directly from the trans-Golgi-network, without first travelling to the cell membrane.

Cell surface CD1 molecules are internalized according to two distinct mechanisms. Specifically, CD1a molecules, which lack a tyrosine-based internalization motif, are internalized to the early endosomes [89] through a clathrin/dynamin-independent manner and recycle back to the plasma membrane through a mechanism that relies on small GTPases, such as Rab22 and ADP-ribosylation factor 6. Both CD1b and CD1c molecules, instead, have a tyrosine-based motif in their cytoplasmic tail and are internalized through clathrin-coated pits via the adaptor protein 2 (AP-2). Thereafter, CD1b is transported to the late endosomes and, after binding to AP-3, traffics to the lysosomes and then recycles to the plasma membrane. On the other hand, CD1c, after reaching the sorting endosomes, routes to the early endosomes, and, although to a lesser extent, to the late endosomes and lysosomes, and then recycles to the plasma membrane. It follows that CD1c operates a comprehensive survey for lipid antigens throughout the endocytic system [90].

The entire CD1 recycling pattern reveals that a large variety of molecular targets could be affected by M. tuberculosis. In addition to that, it must be considered that intracellular lipid loading presumably requires the functional intervention of a number of helper and adaptor molecules, including saposins and apolipoproteins [91, 92] and CD1e itself [93, 94]. Moreover, acidic pH promotes lipid binding to CD1b proteins, thus suggesting that pH fluxes during endosomal recycling regulate the conformation of the CD1 heavy chain to control the size and rate of antigen capture [95]. Within this context, it is worth of note the finding that mycobacteria impair phagosome acidification [58] thus reducing the extent of mycobacterial lipids bound to CD1b for T-cell presentation.

5. HIV and CD1 Expression

Interestingly enough, not only the mycobacterial infection, but also HIV or HTLV-1 infection or intracellular presence of HIV products are able to interfere with CD1 expression. For example, HIV-1-Nef was found to interfere with the intracellular trafficking of CD1a [96], although recombinant Nef added to iDCs increases CD1a expression [97]. Moreover, it must be pointed out that viable HIV-1 particles infect target CD4+ T-cells via CD1b+ exosomes [98]. On the other hand, in 30 to 45% of HIV-infected white and African subjects, peripheral blood MOs exposed in vitro to G4 followed by LPS gave rise to CD1a mDCs releasing IL-10 but not IL-12 [99]. In addition, DCs from HTLV-I-infected monocytes fail to present adequate amounts of CD1a glycoprotein [100].

Preliminary investigations of experimental design (ED)-1 type (see ED codes illustrated in Figure 2) performed in our laboratory, revealed also a possible link between HIV infection and CD1 system, presumably relevant to the increased susceptibility of HIV-infected individuals to mycobacteria. A vector expressing tat DNA (PCV-TAT, [101]) under the control of the major adenoviral late protein, and a control empty vector (PCV-0) were kindly provided by Barbara Ensoli MD of the Italian National Institute of Health. Peripheral blood MOs of healthy donors were incubated with G4 alone or with G4 + a supernatant obtained from the human T-cell leukemia line Jurkat transfected with PCV-0 (sup-PCV-0) or with PCV-TAT (sup-PCV-TAT). The results of a representative experiment demonstrated that tat-induced factors released by transfected cells are able to down-regulate CD1b expression. In fact, after 5-day exposure to G4 in vitro, iDCs generated in the absence of supernatants or in the presence of sup-PCV-0 showed 72% and 79% CD1b+ cells, respectively. In contrast, when iDCs were generated in the presence of sup-PCV-TAT, the percentage of CD1b+cells dropped significantly to 54% (Franzese et al., in preparation). Moreover, if monoclonal antibodies against IL-10 were added to G4 + sup-PCV-TAT at the onset of iDC generation, the percentage of CD1b+ cells raised to 81%. These results along with previous findings indicating that TAT induces IL-10 in MOs [102] and that IL-10 downregulates CD1 expression [7476, 103106], are consistent with the hypothesis that IL-10, generated in the presence of TAT, plays a critical role in compromising CD1b expression.

6. Chemical, Biological, and Physical Agents Affecting CD1 Expression

6.1. Drugs

A number of natural and synthetic compounds of pharmacological interest are able to modulate the expression level of Group I CD1 proteins on immature and/or mature DCs, either in vitro and in vivo, as reported in Table 2.

Table 2
Pharmacological modulation of CD1 molecule expression.

As expected, most of the immunosuppressant and anti-inflammatory agents, including corticosteroids, nonsteroidal anti-inflammatory drugs (NSAID), and anti-asthma compounds, down-regulate cytokine-induced CD1 expression of MOs and impair their functional activity. However, local application of Pimecrolimus on skin in atopic dermatitis, is followed by increase in the number of CD1a+ cells. Moreover, in vitro exposure of CD34+ peripheral blood progenitor cells to Tacrolimus favors the expression of CD1a induced by 14-day treatment with cytokines. Notable exceptions to the inhibitory effects of anti-inflammatory drugs is also represented by Piceatannol (a stylbene compound similar to resveratrol) and terpenes that were found to increase CD1a expression after G4 treatment in vitro of MOs obtained from healthy donors. Of sensible relevance to the problem of MS therapy and identification of disease pathogenesis is the finding that Glatiramer acetate (GA), alone or in combination with IFNβ, is able to down-regulate CD1 expression in vitro or in vivo. Similar inhibitory effects have been described in vitro with vitamin D3 that shows beneficial effects in MS management. These observations appear to provide further support to the hypothesis that significant participation of CD1-restricted T-cell responses against self lipid antigens is involved in the neuronal damage occurring in MS.

Among chemotherapeutic agents, antitubercular (rifampicin) or antiretroviral (entecavir) drugs tend to up-regulate CD1 expression, whereas zidovudine (AZT), that inhibits iDC proliferation, diminishes the overall availability of CD1a+ cells. In the area of antineoplastic therapy, reduction of cytokine-induced CD1 levels by various agents is the dominant finding, as shown in vitro by histone deacetylase (HDAC) inhibitors, tyrosin kinase inhibitors (i.e., imatinib and sorafenib) and antiestrogens, and in vivo by thalidomide in multiple myeloma (MM) patients.

More difficult to interpret is the activity of a classical agent largely utilized in mood disorders including bipolar affective disorders, such as lithium. The drug downregulates the in vitro cytokine-induced CD1a expression in MOs of healthy donors. However, limited CD1a expression is elicited by G4 in MOs collected from patients with bipolar disorders. In this case, in vivo treatment of donor patients with lithium restores full responsiveness of their MOs to G4 exposure in vitro.

6.2. Cytokines and Autacoids

Table 3 illustrates the limited information available from the literature on the effect of prostaglandins and serotonin on CD1a expression in different experimental conditions in vitro. In all cases, the agents show suppressive activity.

Table 3
Effect of autacoids or cytokines on CD1 molecule expression.

When cytokines are considered, GM-CSF and IL-4 are not enlisted in Table 3. Actually, this cytokine combination is used by most of in vitro tests, to induce iDCs that express high levels of CD1 proteins (Figures (Figures11 and and2).2). In particular, GM-CSF is the most potent inducer, whereas IL-4 reinforces the effect of GM-CSF but is scarcely active if used alone.

A number of data from the literature is presently available on IFNs that show predominant inhibitory effects on CD1 system. While IFNα can be involved in the transition from iDCs to mDCs (Figure 1), IFNβ downregulates CD1 protein expression either in vivo or in vitro. In addition this cytokine was found to reduce the functional activity of mDCs. Since IFNβ has acquired a definite role in MS treatment, these results add further support to the hypothesis of the involvement of CD1 system in MS pathogenesis.

Consistent inhibitory effects on CD1 expression are manifested by IL-6 and IL-10 in various experimental conditions. It must be pointed out that in many cases down-regulation of G4-induced CD1 expression provoked by various agents appears to be mediated by the release of IL-6 and more frequently by the release of IL-10 that operates according to an autocrine pattern.

Of interest, finally is the mechanism by which TGFβ appears to maintain CD1a expression on LC generated in vitro from purified CD34+ cells. In this case, the expression of CD1a, that is normally found to be elevated in immature LCs, declines with LC maturation. Since TGFβ prevents LC maturation, it allows the long-term presence of high CD1a levels in LCs.

6.3. Biological and Physical Agents

With the exception of the placental growth factor, all biological and physical agents illustrated in Table 4 provoke down-regulation of cytokine-induced CD1 protein expression. The mechanism underlying the effect of various lipids including some contained in human serum, indicates a common target consisting in peroxisome proliferator-activated receptor (PPAR)γ that appears to be activated by these molecules in various experimental conditions. The observation that human serum, either for the presence of different lipoproteins or for the presence of IgG and β2-microglobulin (Table 4), provides inhibitory effects, poses undoubtedly the question of the efficiency of the CD1 system in vivo in infected patients.

Table 4
Effect of biological or physical agents on CD1 molecule expression.

Of considerable interest is the finding that various supernatants of human tumor cell cultures contain inhibitory factors. Although mycoplasma contamination of cultured cells could be, at least in part, responsible for these findings (see Table 5), it cannot be excluded that this type of suppression of antigen-presenting function could be of relevance in tumor-induced immune suppression.

Table 5
Influence exerted by infectious agents or microorganism products on group 1 CD1 antigen expression.

The in vivo impairment of CD1a expression by ultraviolet light is not surprising, since the general immune-suppressive effects of this type of radiation has been demonstrated in different effector functions of the immune system.

6.4. Infectious Agents or Microorganism Products

In vitro and in vivo studies concerning modulation of CD1 system by bacterial and chlamydial infections generally demonstrated a CD1 upregulation (Table 5). It is reasonable to speculate that, in certain experimental conditions, TLR-2 activation by microorganisms could be involved [29]. Surprisingly, however, is the finding that antral biopsies performed in H. pilori-infected children reveal CD1a/b upregulation respect to normal subjects, whereas in vitro exposure of MOs to formalin-killed H. pilori prevents CD1 induction by G4.

Of particular note is the finding that CD1a is up-regulated in vitro by G4 more vigorously in MOs obtained from MS patients bearing an infectious disease, with respect to MOs obtained from noninfected MS patients. This observation has been put in relationship with the clinical finding that subjects affected by MS are at particular risk of relapse in the course of bacterial infections. Again, this seems to provide support to the hypothesis of a significant role that could be played by CD1 system in MS.

Differently from the in vivo and in vitro effect of the bacteria and chlamydia reported in Table 5, infections with various protozoa, with at least two types of helminthes, and viruses such as HHV-8 and Cytomegalovirus leads to impairment of CD1 expression in various types of experimental design. This is not surprising since the general immunodepressive activity of these infections has been known for several years.

When microorganism products are considered, only attenuated Dengue-2 live vaccine, malaria-associated AMA-1, and staphylococcus superantigen are able to up-regulate cytokine-induced CD1 expression. Toxins and malaria hemozoin provide opposite effects on the system. A particular feature that distinguishes the activity of pertussis toxin from the other microorganism products resides in its unusual property of suppressing CD1a expression selectively, without reducing the levels of the other components of the system (i.e., CD1b and CD1c). It is not excluded that this could allow selective analysis of CD1A gene regulation distinct from that of the other CD1 genes.

Finally, of relevance is the finding that LPS is able to down-regulate G4-induced CD1a. LPS, that is considered the standard agent for generating mDCs from iDCs (Figures (Figures11 and and2),2), is a common constituent of pathogenic or nonpathogenic microorganisms, being present in the cell wall of gram-negative bacteria. Therefore, it is reasonable to consider that this molecule could play a significant role in the clinic, possibly through its modulating activity on CD1 expression and DC maturation.

7. Conclusions and Perspectives

Fine tuning of biological functions governed by a complex signaling network is commonly seen in living organisms, and the CD1 system does not represent an exception to this rule. This opens up several options to intentionally manipulate the CD1 expression in order to enhance or depress antigenic lipid presentation according to the therapeutic needs. The results of the literature analysis presented here clearly demonstrate that a large variety of different externally acting agents, either of synthetic or natural origin, can affect profoundly the expression levels of CD1 glycoproteins, with a possible consequence on DC-mediated lipid presentation to T-cells. Actually, Group I CD1 glycoproteins are mainly involved in the presentation of M. tuberculosis-derived lipids to CD1-restricted T-cells. Pharmacological amplification of the system could provide a significant help for vaccination and treatment modalities concerning millions of subjects presently exposed to tuberculosis threat. In particular, the rapidly expanding area of small RNAs capable of controlling directly or indirectly the expression level of an extremely high numbers of genes, could be carefully considered for planning new types of antimycobacterial vaccines. It is reasonable to predict that properly designed siRNA(s) could be combined in a near future, with BCG or BCG-like vaccines in order to obtain gene silencing vaccines able to inactivate the intracellular signals responsible of Group I CD1 protein suppression.


This work was supported by a grant for tuberculosis investigations provided by the “Provincia di Roma”, Rome, Italy.


Acylated sulfoglycolipid
Antigen-presenting cells
Acetylsalicylic acid
Activating transcription factor
All trans-retinoic acid
Bacillus Calmette-Guerin
Beclomethasone dipropionate
cAMP response element
CRE-binding protein
Dendritic cells
Extracellular signal-regulated kinases
Glatiramer acetate
Granulocyte-macrophage colony stimulating factor
Gold sodium thiomalate
Histone deacetylases
Immature dendritic cells
Langerhans cells
Mitogen-activated protein kinase
Mature dendritic cells
Multidrug resistance
Multiple myeloma
Multidrug resistance protein 1
Multiple sclerosis
Microsomal triglyceride transfer protein
Niflumic acid
Nonsteroidal anti-inflammatory drugs
Peripheral blood mononuclear cells
Peroxisome proliferator-activated receptor
Rheumatoid arthritis
T-cell receptor
Toll-like receptors
Tumor necrosis factor.


1. Lin PG, Flynn JL. Understanding latent tuberculosis: a moving target. Journal of Immunology. 2010;185(1):15–22. [PMC free article] [PubMed]
2. Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR. An essential role for interferon γ in resistance to Mycobacterium tuberculosis infection. Journal of Experimental Medicine. 1993;178(6):2249–2254. [PMC free article] [PubMed]
3. Porcelli S, Brenner MB, Greenstein JL, Balk SP, Terhorst C, Bleicher PA. Recognition of cluster of differentiation 1 antigens by human CD4 CD8 cytolytic T lymphocytes. Nature. 1989;341(6241):447–450. [PubMed]
4. Porcelli S, Morita CT, Brenner MB. CD1b restricts the response of human CD4CD8 T lymphocytes to a microbial antigen. Nature. 1992;360(6404):593–597. [PubMed]
5. Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB. Recognition of lipid antigen by CD1-restricted αβ+ T cells. Nature. 1994;372(6507):691–694. [PubMed]
6. Cohen NR, Garg S, Brenner MB. Chapter 1 antigen presentation by CD1. Lipids, T cells, and NKT cells in microbial immunity. Advances in Immunology. 2009;102:1–94. [PubMed]
7. Taniguchi M, Nakayama T. Recognition and function of Vα14 NKT cells. Seminars in Immunology. 2000;12(6):543–550. [PubMed]
8. Betel D, Koppal A, Agius P, Sander C, Leslie C. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biology. 2010;11 , article R90 [PMC free article] [PubMed]
9. Kasinrerk W, Baumruker T, Majdic O, Knapp W, Stockinger H. CD1 molecule expression on human monocytes induced by granulocyte- macrophage colony-stimulating factor. Journal of Immunology. 1993;150(2):579–584. [PubMed]
10. Porcelli SA, Modlin RL. The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annual Review of Immunology. 1999;17:297–329. [PubMed]
11. Schaible UE, Hagens K, Fischer K, Collins HL, Kaufmann SHE. Intersection of group I CD1 molecules and mycobacteria in different intracellular compartments of dendritic cells. Journal of Immunology. 2000;164(9):4843–4852. [PubMed]
12. Salio M, Silk JD, Cerundolo V. Recent advances in processing and presentation of CD1 bound lipid antigens. Current Opinion in Immunology. 2010;22(1):81–88. [PubMed]
13. Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB. Recognition of lipid antigen by CD1-restricted αβ T cells. Nature. 1994;372(6507):691–694. [PubMed]
14. Porcelli SA. The CD1 family: a third lineage of antigen-presenting molecules. Advances in Immunology. 1995;59:1–98. [PubMed]
15. Stenger S, Mazzaccaro RJ, Uyemura K, et al. Differential effects of cytolytic T cell subsets on intracellular infection. Science. 1997;276(5319):1684–1687. [PubMed]
16. Sieling PA, Ochoa MT, Jullien D, et al. Evidence for human CD4 T cells in the CD1-restricted repertoire: derivation of mycobacteria-reactive T cells from leprosy lesions. Journal of Immunology. 2000;164(9):4790–4796. [PubMed]
17. Cui Y, Kang L, Cui L, He W. Human γδ T cell Recognition of lipid A is predominately presented by CD1b or CD1c on dendritic cells. Biology Direct. 2009;4, article 47 [PMC free article] [PubMed]
18. Thoma-Uszynski S, Stenger S, Modlin RL. CTL-mediated killing of intracellular Mycobacterium tuberculosis is independent of target cell nuclear apoptosis. Journal of Immunology. 2000;165(10):5773–5779. [PubMed]
19. Brigl M, Brenner MB. CD1: antigen presentation and T cell function. Annual Review of Immunology. 2004;22:817–890. [PubMed]
20. Vincent MS, Gumperz JE, Brenner MB. Understanding the function of CD1-restricted T cells. Nature Immunology. 2003;4(6):517–523. [PubMed]
21. Méndez-Samperio P. Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease. International Journal of Infectious Diseases. 2010;14(5):e366–e371. [PubMed]
22. De Libero G, Mori L. Structure and biology of self lipid antigens. Current Topics in Microbiology and Immunology. 2007;314:51–72. [PubMed]
23. Blewett MM. Lipid autoreactivity in multiple sclerosis. Medical Hypotheses. 2010;74(3):433–442. [PubMed]
24. Dascher CC, Hiromatsu K, Xiong X, et al. Immunization with a mycobacterial lipid vaccine improves pulmonary pathology in the guinea pig model of tuberculosis. International Immunology. 2003;15(8):915–925. [PubMed]
25. Hiromatsu K, Dascher CC, LeClair KP, et al. Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens. Journal of Immunology. 2002;169(1):330–339. [PubMed]
26. Felio K, Nguyen H, Dascher CC, et al. CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice. Journal of Experimental Medicine. 2009;206(11):2497–2509. [PMC free article] [PubMed]
27. Colmone A, Li S, Wang CR. Activating transcription factor/cAMP response element binding protein family member regulated transcription of CD1A. Journal of Immunology. 2006;177(10):7024–7032. [PubMed]
28. Niwano K, Arai M, Koitabashi N, et al. Competitive binding of CREB and ATF2 to cAMP/ATF responsive element regulates eNOS gene expression in endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26(5):1036–1042. [PubMed]
29. Havelange V, Garzon R. Micrornas: emerging key regulators of hematopoiesis. American Journal of Hematology. 2010;85(12):935–942. [PubMed]
30. Cobb BS, Hertweck A, Smith J, et al. A role for Dicer in immune regulation. Journal of Experimental Medicine. 2006;203(11):2519–2527. [PMC free article] [PubMed]
31. Lindsay MA. microRNAs and the immune response. Trends in Immunology. 2008;29(7):343–351. [PubMed]
32. Recchiuti A, Krishnamoorthy S, Fredman G, et al. MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits. FASEB Journal. 2011;25(2):544–560. [PubMed]
33. Kuipers H, Schnorfeil FM, Fehling H-J, Bartels H, Brocker T. Dicer-dependent microRNAs control maturation, function, and maintenance of Langerhans cells in vivo. Journal of Immunology. 2010;185(1):400–409. [PubMed]
34. Ros VID, Hurst GDD. Lateral gene transfer between prokaryotes and multicellular eukaryotes: ongoing and significant? BMC Biology. 2009;7, article 20 [PMC free article] [PubMed]
35. DiChiara JM, Contreras-Martinez LM, Livny J, Smith D, McDonough KA, Belfort M. Multiple small RNAs identified in Mycobacterium bovis BCG are also expressed in Mycobacterium tuberculosis and Mycobacterium smegmatis. Nucleic Acids Research. 2010;38(12):4067–4078. [PMC free article] [PubMed]
36. Akama T, Suzuki K, Tanigawa K, et al. Whole-genome tiling array analysis of Mycobacterium leprae RNA reveals high expression of pseudogenes and noncoding regions. Journal of Bacteriology. 2009;191(10):3321–3327. [PMC free article] [PubMed]
37. Watanabe Y, Watari E, Matsunaga I, et al. BCG vaccine elicits both T-cell mediated and humoral immune responses directed against mycobacterial lipid components. Vaccine. 2006;24(29-30):5700–5707. [PubMed]
38. Liu J, Tran V, Leung AS, Alexander DC, Zhu B. BCG vaccines: their mechanisms of attenuation and impact on safety and protective efficacy. Human Vaccines. 2009;5(2):70–78. [PubMed]
39. Barker LF, Brennan MJ, Rosenstein PK, Sadoff JC. Tuberculosis vaccine research: the impact of immunology. Current Opinion in Immunology. 2009;21(3):331–338. [PubMed]
40. Alderwick LJ, Birch HL, Mishra AK, Eggeling L, Besra GS. Structure, function and biosynthesis of the Mycobacterium tuberculosis cell wall: arabinogalactan and lipoarabinomannan assembly with a view to discovering new drug targets. Biochemical Society Transactions. 2007;35(5):1325–1328. [PubMed]
41. Moody DB, Young DC, Cheng TY, et al. T cell activation by lipopeptide antigens. Science. 2004;303(5657):527–531. [PubMed]
42. Moody DB, Ulrichs T, Mühlecker W, et al. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000;404(6780):884–888. [PubMed]
43. Gilleron M, Stenger S, Mazorra Z, et al. Diacylated sulfoglycolipids are novel mycobacterial antigens stimulating CD1-restricted T Cells during Infection with Mycobacterium tuberculosis. Journal of Experimental Medicine. 2004;199(5):649–659. [PMC free article] [PubMed]
44. De Libero G, Mori L. Recognition of lipid antigens by T cells. Nature Reviews Immunology. 2005;5(6):485–496. [PubMed]
45. Guiard J, Collmann A, Garcia-Alles LF, et al. Fatty acyl structures of Mycobacterium tuberculosis sulfoglycolipid govern T cell response. Journal of Immunology. 2009;182(11):7030–7037. [PubMed]
46. Kasmar A, Van Rhijn I, Moody DB. The evolved functions of CD1 during infection. Current Opinion in Immunology. 2009;21(4):397–403. [PMC free article] [PubMed]
47. Sieling PA, Jullien D, Dahlem M, et al. CD1 expression by dendritic cells in human leprosy lesions: correlation with effective host immunity. Journal of Immunology. 1999;162(3):1851–1858. [PubMed]
48. Barker LF, Brennan MJ, Rosenstein PK, Sadoff JC. Tuberculosis vaccine research: the impact of immunology. Current Opinion in Immunology. 2009;21(3):331–338. [PubMed]
49. Sieling PA, Torrelles JB, Stenger S, et al. The human CD1-restricted T cell repertoire is limited to cross-reactive antigens: implications for host responses against immunologically related pathogens. Journal of Immunology. 2005;174(5):2637–2644. [PubMed]
50. Ulrichs T, Moody DB, Grant E, Kaufmann SHE, Porcelli SA. T-cell responses to CD1-presented lipid antigens in humans with Mycobacterium tuberculosis infection. Infection and Immunity. 2003;71(6):3076–3087. [PMC free article] [PubMed]
51. Chen X, Zhou B, Li M, et al. CD4+CD25+FoxP3+ regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clinical Immunology. 2007;123(1):50–59. [PubMed]
52. Vincent MS, Xiong X, Grant EP, Peng W, Brenner MB. CD1a-, b-, and c-restricted TCRs recognize both self and foreign antigens. Journal of Immunology. 2005;175(10):6344–6351. [PubMed]
53. Nguyen TKA, Koets AP, Santema WJ, van Eden W, Rutten VPMG, Van Rhijn I. The mycobacterial glycolipid glucose monomycolate induces a memory T cell response comparable to a model protein antigen and no B cell response upon experimental vaccination of cattle. Vaccine. 2009;27(35):4818–4825. [PMC free article] [PubMed]
54. Kaufmann SHE. Protection against tuberculosis: cytokines, T cells, and macrophages. Annals of the Rheumatic Diseases. 2002;61(2):ii54–ii58. [PMC free article] [PubMed]
55. Lee J, Kornfeld H. Interferon-γ regulates the death of M. tuberculosis-infected macrophages. Journal of Cell Death . 2010;3:1–11. [PMC free article] [PubMed]
56. Baena A, Porcelli SA. Evasion and subversion of antigen presentation by Mycobacterium tuberculosis. Tissue Antigens. 2009;74(3):189–204. [PMC free article] [PubMed]
57. González-Juarrero M, O'Sullivan MP. Optimization of inhaled therapies for tuberculosis: the role of macrophages and dendritic cells. Tuberculosis. 2011;91(1):86–92. [PubMed]
58. Meena LS, Rajni T. Survival mechanisms of pathogenic Mycobacterium tuberculosis H37 Rv. FEBS Journal. 2010;277(11):2416–2427. [PubMed]
59. Lang ML, Glatman-Freedman A. Do CD1-restricted T cells contribute to antibody-mediated immunity against Mycobacterium tuberculosis? Infection and Immunity. 2006;74(2):803–809. [PMC free article] [PubMed]
60. Jayachandran R, Sundaramurthy V, Combaluzier B, et al. Survival of Mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin. Cell. 2007;130(1):37–50. [PubMed]
61. Winau F, Kaufmann SHE, Schaible UE. Apoptosis paves the detour path for CD8T cell activation against intracellular bacteria. Cellular Microbiology. 2004;6(7):599–607. [PubMed]
62. Danelishvili L, Yamazaki Y, Selker J, Bermudez LE. Secreted Mycobacterium tuberculosis Rv3654c and Rv3655c proteins participate in the suppression of macrophage apoptosis. PLoS ONE. 2010;5(5) Article ID e10474. [PMC free article] [PubMed]
63. Stenger S, Niazi KR, Modlin RL. Down-regulation of CD1 on antigen-presenting cells by infection with Mycobacterium tuberculosis. Journal of Immunology. 1998;161(7):3582–3588. [PubMed]
64. Prete SP, Girolomoni G, Giuliani A, et al. Limited introduction of CD1b expression by BCG in human adherent mononuclear cells is mediated by GM-CSF. Journal of Chemotherapy. 2000;12(supplement 6):p. 146.
65. Roura-Mir C, Wang L, Cheng TY, et al. Mycobacterium tuberculosis regulates CD1 antigen presentation pathways through TLR-2. Journal of Immunology. 2005;175(3):1758–1766. [PubMed]
66. Videira PA, Calais FM, Correia M, et al. Efficacy of Bacille Calmette-Guérin immunotherapy predicted by expression of antigen-presenting molecules and chemokines. Urology. 2009;74(4):944–950. [PubMed]
67. Miranda A, Amadeu TP, Schueler G, et al. Increased Langerhans cell accumulation after mycobacterial stimuli. Histopathology. 2007;51(5):649–656. [PMC free article] [PubMed]
68. Rajashree P, Krishnan G, Das SD. Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis. Tuberculosis. 2009;89(1):77–83. [PubMed]
69. Prete SP, Giuliani A, Iona E, et al. Bacillus Calmette-Guerin down-regulates CD1b induction by granulocyte-macrophage colony stimulating factor in human peripheral blood monocytes. Journal of Chemotherapy. 2001;13(1):52–58. [PubMed]
70. Giuliani A, Prete SP, Graziani G, et al. Influence of Mycobacterium bovis bacillus Calmette Guérin on in vitro induction of CD1 molecules in human adherent mononuclear cells. Infection and Immunity. 2001;69(12):7461–7470. [PMC free article] [PubMed]
71. Mariotti S, Teloni R, Iona E, et al. Mycobacterium tuberculosis subverts the differentiation of human monocytes into dendritic cells. European Journal of Immunology. 2002;32(11):3050–3058. [PubMed]
72. Gagliardi MC, Teloni R, Mariotti S, et al. Bacillus Calmette-Guérin shares with virulent Mycobacterium tuberculosis the capacity to subvert monocyte differentiation into dendritic cell: Implication for its efficacy as a vaccine preventing tuberculosis. Vaccine. 2004;22(29-30):3848–3857. [PubMed]
73. Martino A, Sacchi A, Volpe E, et al. Non-pathogenic Mycobacterium smegmatis induces the differentiation of human monocytes directly into fully mature dendritic cells. Journal of Clinical Immunology. 2005;25(4):365–375. [PubMed]
74. Prete SP, Giuliani A, D’Atri S, et al. BCG-infected adherent mononuclear cells release cytokines that regulate group 1 CD1 molecule expression. International Immunopharmacology. 2007;7(3):321–332. [PubMed]
75. Gagliardi MC, Teloni R, Giannoni F, et al. Mycobacteria exploit p38 signaling to affect CD1 expression and lipid antigen presentation by human dendritic cells. Infection and Immunity. 2009;77(11):4947–4952. [PMC free article] [PubMed]
76. Remoli ME, Giacomini E, Petruccioli E, et al. Bystander inhibition of dendritic cell differentiation by Mycobacterium tuberculosis-induced IL-10. Immunology and Cell Biology. 31 August 2010. [PubMed]
77. Jung SB, Song CH, Yang CS, et al. Role of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the secretion of tumor necrosis factor-α and interleukin-10 by the PPD antigen of Mycobacterium tuberculosis. Journal of Clinical Immunology. 2005;25(5):482–490. [PubMed]
78. Reiling N, Blumenthal A, Flad HD, Ernst M, Ehlers S. Mycobacteria-induced TNF-α and IL-10 formation by human macrophages is differentially regulated at the level of mitogen-activated protein kinase activity. Journal of Immunology. 2001;167(6):3339–3345. [PubMed]
79. Song CH, Lee JS, Lee SH, et al. Role of mitogen-activated protein kinase pathways in the production of tumor necrosis factor-α, interleukin-10, and monocyte chemotactic protein-1 by Mycobacterium tuberculosis H37Rv-infected human monocytes. Journal of Clinical Immunology. 2003;23(3):194–201. [PubMed]
80. Méndez-Samperio P, Trejo A, Pérez A. Mycobacterium bovis Bacillus Calmette-Guérin (BCG) stimulates IL-10 production via the PI3K/Akt and p38 MAPK pathways in human lung epithelial cells. Cellular Immunology. 2008;251(1):37–42. [PubMed]
81. Souza CD, Evanson OA, Weiss DJ. Mitogen activated protein kinase pathway is an important component of the anti-inflammatory response in Mycobacterium avium subsp. paratuberculosis-infected bovine monocytes. Microbial Pathogenesis. 2006;41(2-3):59–66. [PubMed]
82. Cheung BKW, Lee DCW, Li JCB, Lau YUL, Lau ASY. A role for double-stranded RNA-activated protein kinase PKR in Mycobacterium-induced cytokine expression. Journal of Immunology. 2005;175(11):7218–7225. [PubMed]
83. Chan MMP, Cheung BKW, Li JCB, Chan LLY, Lau ASY. A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction. Journal of Leukocyte Biology. 2009;86(2):283–291. [PubMed]
84. Nair S, Ramaswamy PA, Ghosh S, et al. The PPE18 of Mycobacterium tuberculosis interacts with TLR2 and activates IL-10 induction in macrophage. Journal of Immunology. 2009;183(10):6269–6281. [PubMed]
85. Balboa L, Romero MM, Yokobori N, et al. Mycobacterium tuberculosis impairs dendritic cell response by altering CD1b, DC-SIGN and MR profile. Immunology and Cell Biology. 2010;88(7):716–726. [PubMed]
86. Strominger JL. An alternative path for antigen presentation: group 1 CD1 proteins. Journal of Immunology. 2010;184(7):3303–3305. [PubMed]
87. Shamshiev A, Donda A, Prigozy TI, et al. The αβ T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity. 2000;13(2):255–264. [PubMed]
88. Manolova V, Kistowska M, Paoletti S, et al. Functional CD1a is stabilized by exogenous lipids. European Journal of Immunology. 2006;36(5):1083–1092. [PubMed]
89. Cernadas M, Cavallari M, Watts G, Mori L, De Libero G, Brenner MB. Early recycling compartment trafficking of CD1a is essential for its intersection and presentation of lipid antigens. Journal of Immunology. 2010;184(3):1235–1241. [PubMed]
90. Sugita M, van der Wel N, Rogers RA, Peters PJ, Brenner MB. CD1c molecules broadly survey the endocytic system. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(15):8445–8450. [PubMed]
91. Zhou D, Cantu C, III, Sagiv Y, et al. Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science. 2004;303(5657):523–527. [PMC free article] [PubMed]
92. van den Elzen P, Garg S, León L, et al. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature. 2005;437(7060):906–910. [PubMed]
93. de la Salle H, Mariotti S, Angenieux C, et al. Immunology: assistance of microbial glycolipid antigen processing by CD1e. Science. 2005;310(5752):1321–1324. [PubMed]
94. Tourne S, Maitre B, Collmann A, et al. Cutting edge: a naturally occurring mutation in CD1e impairs lipid antigen presentation. Journal of Immunology. 2008;180(6):3642–3646. [PubMed]
95. Relloso M, Cheng TY, Im JS, et al. pH-Dependent Interdomain Tethers of CD1b Regulate Its Antigen Capture. Immunity. 2008;28(6):774–786. [PMC free article] [PubMed]
96. Shinya E, Owaki A, Shimizu M, et al. Endogenously expressed HIV-1 nef down-regulates antigen-presenting molecules, not only class I MHC but also CD1a, in immature dendritic cells. Virology. 2004;326(1):79–89. [PubMed]
97. Quaranta MG, Tritarelli E, Giordani L, Viora M. HIV-1 Nef induces dendritic cell differentiation: a possible mechanism of uninfected CD4+ T cell activation. Experimental Cell Research. 2002;275(2):243–254. [PubMed]
98. Wiley RD, Gummuluru S. Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(3):738–743. [PubMed]
99. Sacchi A, Cappelli G, Cairo C, et al. Differentiation of monocytes into CD1a- dendritic cells correlates with disease progression in HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes. 2007;46(5):519–528. [PubMed]
100. Makino M, Wakamatsu SI, Shimokubo S, Arima N, Baba M. Production of functionally deficient dendritic cells from HTLV-I-infected monocytes: implications for the dendritic cell defect in adult T cell leukemia. Virology. 2000;274(1):140–148. [PubMed]
101. Ensoli B, Buonaguro L, Barillari G, et al. Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. Journal of Virology. 1993;67(1):277–287. [PMC free article] [PubMed]
102. Gee K, Angel JB, Mishra S, Blahoianu MA, Kumar A. IL-10 regulation by HIV-tat in primary human monocytic cells: involvement of calmodulin/calmodulin-dependent protein kinase-activated p38 MAPIC and Sp-1 and CREB-1 transcription factors. Journal of Immunology. 2007;178(2):798–807. [PubMed]
103. De Smedt T, Van Mechelen M, De Becker G, Urbain J, Leo O, Moser M. Effect of interleukin-10 on dendritic cell maturation and function. European Journal of Immunology. 1997;27(5):1229–1235. [PubMed]
104. Buelens C, Verhasselt V, De Groote D, Thielemans K, Goldman M, Willems F. Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. European Journal of Immunology. 1997;27(3):756–762. [PubMed]
105. Allavena P, Piemonti L, Longoni D, et al. IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. European Journal of Immunology. 1998;28(1):359–369. [PubMed]
106. Gerlini G, Tun-Kyi A, Dudli C, Burg G, Pimpinelli N, Nestle FO. Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions. American Journal of Pathology. 2004;165(6):1853–1863. [PubMed]
107. Nahmod KA, Vermeulen ME, Raiden S, et al. Control of dendritic cell differentiation by angiotensin II. The FASEB Journal. 2003;17(3):491–493. [PubMed]
108. Tanaka A, Minoguchi K, Samson KTR, et al. Inhibitory effects of suplatast tosilate on the differentiation and function of monocyte-derived dendritic cells from patients with asthma. Clinical and Experimental Allergy. 2007;37(7):1083–1089. [PubMed]
109. Knijff EM, Ruwhof C, De Wit HJ, et al. Monocyte-derived dendritic cells in bipolar disorder. Biological Psychiatry. 2006;59(4):317–326. [PubMed]
110. Liu K-J, Lee Y-L, Yang Y-Y, et al. Modulation of the development of human monocyte-derived dendritic cells by lithium chloride. Journal of Cellular Physiology. 2011;226(2):424–433. [PubMed]
111. Komi J, Lassila O. Nonsteroidal anti-estrogens inhibit the functional differentiation of human monocyte-derived dendritic cells. Blood. 2000;95(9):2875–2882. [PubMed]
112. Möller GM, Overbeek SE, Van Helden-Meeuwsen CG, et al. Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clinical and Experimental Allergy. 1996;26(5):517–524. [PubMed]
113. Xia CQ, Peng R, Beato F, Clare-Salzler MJ. Dexamethasone induces IL-10-producing monocyte-derived dendritic cells with durable immaturity. Scandinavian Journal of Immunology. 2005;62(1):45–54. [PubMed]
114. Mainali ES, Tew JG. Dexamethasone selectively inhibits differentiation of cord blood stem cell derived-dendritic cell (DC) precursors into immature DCs. Cellular Immunology. 2004;232(1-2):127–136. [PubMed]
115. Mainali ES, Kikuchi T, Tew JG. Dexamethasone inhibits maturation and alters function of monocyte-derived dendritic cells from cord blood. Pediatric Research. 2005;58(1):125–131. [PubMed]
116. Verhoeven GT, Van Haarst JMW, De Wit HJ, Simons PJ, Hoogsteden HC, Drexhage HA. Glucocorticoids hamper the ex vivo maturation of lung dendritic cells from their low autofluorescent precursors in the human bronchoalveolar lavage: decreases in allostimulatory capacity and expression of CD80 and CD86. Clinical and Experimental Immunology. 2000;122(2):232–240. [PubMed]
117. Giuliani A, Porcelli SA, Tentori L, et al. Effect of rifampin on CD1b expression and double-negative T cell responses against mycobacteria-derived glycolipid antigen. Life Sciences. 1998;63(12):985–994. [PubMed]
118. Tentori L, Graziani G, Porcelli SA, et al. Rifampin increases cytokine-induced expression of the CD1b molecule in human peripheral blood monocytes. Antimicrobial Agents and Chemotherapy. 1998;42(3):550–554. [PMC free article] [PubMed]
119. Giuliani A, Tentori L, Pepponi R, et al. Cytokine-induced expression of CD1b molecules by peripheral blood monocytes: influence of 3′-azido-3′-deoxythymidine. Pharmacological Research. 1997;35(2):135–140. [PubMed]
120. Lu GF, Tang FA, Zheng PY, Yang PC, Qi YM. Entecavir up-regulates dendritic cell function in patients with chronic hepatitis B. World Journal of Gastroenterology. 2008;14(10):1617–1621. [PMC free article] [PubMed]
121. Chen YJ, Chao KSC, Yang YC, Hsu ML, Lin CP, Chen YY. Zoledronic acid, an aminobisphosphonate, modulates differentiation and maturation of human dendritic cells. Immunopharmacology and Immunotoxicology. 2009;31(3):499–508. [PubMed]
122. den Dekker E, Grefte S, Huijs T, et al. Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells. Journal of Immunology. 2008;180(6):3680–3688. [PubMed]
123. Nencioni A, Beck J, Werth D, et al. Histone deacetylase inhibitors affect dendritic cell differentiation and immunogenicity. Clinical Cancer Research. 2007;13(13):3933–3941. [PubMed]
124. Nascimento CR, Freire-de-Lima CG, da Silva de Oliveira A, Rumjanek FD, Rumjanek VM. The short chain fatty acid sodium butyrate regulates the induction of CD1a in developing dendritic cells. Immunobiology. 2011;216(3):275–284. [PubMed]
125. Smith KJ, Hamza S, Skelton H. Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern. Clinical and Experimental Dermatology. 2004;29(5):505–512. [PubMed]
126. Shu YQ, Gu Y. The effect ofdendritic cells activated byOK-432and pulsed with antigens oncytokine induced killers. Biomedicine and Pharmacotherapy. 2006;60(4):156–160. [PubMed]
127. Wang ZY, Morinobu A, Kawano S, Saegusa J, Wang B, Kumagai S. Gold sodium thiomalate suppresses the differentiation and function of human dendritic cells from peripheral blood monocytes. Clinical and Experimental Rheumatology. 2002;20(5):683–688. [PubMed]
128. Ruggieri M, Pica C, Lia A, et al. Combination treatment of glatiramer acetate and minocycline affects phenotype expression of blood monocyte-derived dendritic cells in Multiple Sclerosis patients. Journal of Neuroimmunology. 2008;197(2):140–146. [PubMed]
129. Hussein Y, Sanna A, Söderström M, Link H, Huang YM. Multiple sclerosis: expression of CDIa and production of IL-12 p70 and IFN-γ by blood mononuclear cells in patients on combination therapy with IFN-β and glatiramer acetate compared to monotherapy with IFN-β Multiple Sclerosis. 2004;10(1):16–25. [PubMed]
130. Hussien Y, Sanna A, Söderström M, Link H, Huang YUM. Glatiramer acetate and IFN-β act on dendritic cells in multiple sclerosis. Journal of Neuroimmunology. 2001;121(1-2):102–110. [PubMed]
131. Litjens NHR, Rademaker M, Ravensbergen B, Thio HB, Van Dissel JT, Nibbering PH. Effects of monomethylfumarate on dendritic cell differentiation. British Journal of Dermatology. 2006;154(2):211–217. [PubMed]
132. Kalthoff FS, Chung J, Musser P, Stuetz A. Pimecrolimus does not affect the differentiation, maturation and function of human monocyte-derived dendritic cells, in contrast to corticosteroids. Clinical and Experimental Immunology. 2003;133(3):350–359. [PubMed]
133. Simon D, Vassina E, Yousefi S, Braathen LR, Simon HU. Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment. Allergy. 2005;60(7):944–951. [PubMed]
134. Monti P, Mercalli A, Leone BE, Valerio DC, Allavena P, Piemonti L. Rapamycin impairs antigen uptake of human dendritic cells. Transplantation. 2003;75(1):137–145. [PubMed]
135. Chen Y, Yang C, Jin N, et al. Sinomenine promotes differentiation but impedes maturation and co-stimulatory molecule expression of human monocyte-derived dendritic cells. International Immunopharmacology. 2007;7(8):1102–1110. [PubMed]
136. Cos J, Villalba T, Parra R, et al. FK506 in the maturation of dendritic cells. Haematologica. 2002;87(7):679–687. [PubMed]
137. Wollenberg A, Sharma S, von Bubnoff D, Geiger E, Haberstok J, Bieber T. Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis. Journal of Allergy and Clinical Immunology. 2001;107(3):519–525. [PubMed]
138. Shimizu K, Fujii SI, Fujimoto K, Kawa K, Yamada A, Kawano F. Tacrolimus (FK506) treatment of CD34+ hematopoietic progenitor cells promote the development of dendritic cells that drive CD4+ T cells toward Th2 responses. Journal of Leukocyte Biology. 2000;68(5):633–640. [PubMed]
139. Zhu KJ, Shen QY, Cheng H, Mao XH, Lao LIM, Hao GL. Triptolide affects the differentiation, maturation and function of human dendritic cells. International Immunopharmacology. 2005;5(9):1415–1426. [PubMed]
140. Del Prete A, Zaccagnino P, Di Paola M, et al. Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions. Free Radical Biology and Medicine. 2008;44(7):1443–1451. [PubMed]
141. van de Ven R, de Jong MC, Reurs AW, et al. Dendritic cells require multidrug resistance protein 1 (ABCC1) transporter activity for differentiation. Journal of Immunology. 2006;176(9):5191–5198. [PubMed]
142. Bedini C, Nasorri F, Girolomoni G, De Pità O, Cavani A. Antitumour necrosis factor-α chimeric antibody (infliximab) inhibits activation of skin-homing CD4+ and CD8+ T lymphocytes and impairs dendritic cell function. British Journal of Dermatology. 2007;157(2):249–258. [PubMed]
143. Bufan B, Mojsilović S, Vučićević D, et al. Comparative effects of aspirin and NO-releasing aspirins on differentiation, maturation and function of human monocyte-derived dendritic cells in vitro. International Immunopharmacology. 2009;9(7-8):910–917. [PubMed]
144. Švajger U, Vidmar A, Jeras M. Niflumic acid renders dendritic cells tolerogenic and up-regulates inhibitory molecules ILT3 and ILT4. International Immunopharmacology. 2008;8(7):997–1005. [PubMed]
145. Kaser A, Hava DL, Dougan SK, et al. Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules. European Journal of Immunology. 2008;38(8):2351–2359. [PubMed]
146. Fernández-Ruiz V, González A, López-Moratalla N. Effect of nitric oxide in the differentiation of human monocytes to dendritic cells. Immunology Letters. 2004;93(1):87–95. [PubMed]
147. López P, Gutiérrez C, Suárez A, et al. IFNα treatment generates antigen-presenting cells insensitive to atorvastatin inhibition of MHC-II expression. Clinical Immunology. 2008;129(2):350–359. [PubMed]
148. Bartosik-Psujek H, Tabarkiewicz J, Pocinska K, Radej S, Stelmasiak Z, Rolinski J. Immunomodulatory effects of IFN-β and lovastatin on immunophenotype of monocyte-derived dendritic cells in multiple sclerosis. Archivum Immunologiae et Therapiae Experimentalis. 2010;58(4):313–319. [PubMed]
149. Sioud M, Fløisand Y. TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1-type response. European Journal of Immunology. 2007;37(10):2834–2846. [PubMed]
150. Appel S, Rupf A, Weck MM, et al. Effects of imatinib on monocyte-derived dendritic cells are mediated by inhibition of nuclear factor-κB and Akt signaling pathways. Clinical Cancer Research. 2005;11(5):1928–1940. [PubMed]
151. Appel S, Boehmler AM, Grünebach F, et al. Imatinib mesylate affects the development and function of dendritic cells generated from CD34+ peripheral blood progenitor cells. Blood. 2004;103(2):538–544. [PubMed]
152. Hipp MM, Hilf N, Walter S, et al. Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses. Blood. 2008;111(12):5610–5620. [PubMed]
153. Mohty M, Morbelli S, Isnardon D, et al. All-trans retinoic acid skews monocyte differentiation into interleukin-12-secreting dendritic-like cells. British Journal of Haematology. 2003;122(5):829–836. [PubMed]
154. Wada Y, Hisamatsu T, Kamada N, Okamoto S, Hibi T. Retinoic acid contributes to the induction of IL-12-hypoproducing dendritic cells. Inflammatory Bowel Diseases. 2009;15(10):1548–1556. [PubMed]
155. Schütt P, Buttkereit U, Brandhorst D, et al. In vitro dendritic cell generation and lymphocyte subsets in myeloma patients: influence of thalidomide and high-dose chemotherapy treatment. Cancer Immunology, Immunotherapy. 2005;54(5):506–512. [PubMed]
156. Oliver SJ, Kikuchi T, Krueger JG, Kaplan G. Thalidomide induces granuloma differentiation in sarcoid skin lesions associated with disease improvement. Clinical Immunology. 2002;102(3):225–236. [PubMed]
157. Coven TR, Murphy FP, Gilleaudeau P, Cardinale I, Krueger JG. Trimethylpsoralen bath PUVA is a remittive treatment for psoriasis vulgaris: evidence that epidermal immunocytes are direct therapeutic targets. Archives of Dermatology. 1998;134(10):1263–1268. [PubMed]
158. Canning MO, Grotenhuis K, de Wit HJ, Drexhage HA. Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells. European Journal of Endocrinology. 2000;143(5):687–695. [PubMed]
159. Takei M, Umeyama A, Arihara S. T-cadinol and calamenene induce dendritic cells from human monocytes and drive Th1 polarization. European Journal of Pharmacology. 2006;537(1–3):190–199. [PubMed]
160. Takei M, Umeyama A, Arihara S. Epicubenol and Ferruginol induce DC from human monocytes and differentiate IL-10-producing regulatory T cells in vitro. Biochemical and Biophysical Research Communications. 2005;337(2):730–738. [PubMed]
161. Takei M, Umeyama A, Arihara S, Matsumoto H. Effect of piceatannol in human monocyte-derived dendritic cells in vitro. Journal of Pharmaceutical Sciences. 2005;94(5):974–982. [PubMed]
162. Takei M, Tachikawa E, Hasegawa H, Lee J-J. Dendritic cells maturation promoted by M1 and M4, end products of steroidal ginseng saponins metabolized in digestive tracts, drive a potent Th1 polarization. Biochemical Pharmacology. 2004;68(3):441–452. [PubMed]
163. Canning MO, Grotenhuis K, de Wit H, Ruwholf C, Drexhage HA. 1-α,25-dihydroxyvitamin D3 (1,25(OH)2D3) hampers the maturation of fully active immature dendritic cells from monocytes. European Journal of Endocrinology. 2001;145(3):351–357. [PubMed]
164. Berer A, Stöckl J, Majdic O, et al. 1,25-Dihydroxyvitamin D3 inhibits dendritic cell differentiation and maturation in vitro. Experimental Hematology. 2000;28(5):575–583. [PubMed]
165. Bartosik-Psujek H, Tabarkiewicz J, Pocinska K, Stelmasiak Z, Rolinski J. Immunomodulatory effects of vitamin D3 on monocyte-derived dendritic cells in multiple sclerosis. Multiple Sclerosis. 2010;16(12):1513–1516. [PubMed]
166. Pedersen AW, Holmstrøm K, Jensen SS, et al. Phenotypic and functional markers for 1α,25-dihydroxyvitamin D3 -modified regulatory dendritic cells. Clinical and Experimental Immunology. 2009;157(1):48–59. [PubMed]
167. Zhu K, Gläser R, Mrowietz U. Vitamin D3 and analogues modulate the expression of CSF-1 and its receptor in human dendritic cells. Biochemical and Biophysical Research Communications. 2002;297(5):1211–1217. [PubMed]
168. Piemonti L, Monti P, Sironi M, et al. Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. Journal of Immunology. 2000;164(9):4443–4451. [PubMed]
169. Reichrath J, Müller SM, Kerber A, Baum HP, Bahmer FA. Biologic effects of topical calcipotriol (MC903) treatment in psoriatic skin. Journal of the American Academy of Dermatology. 1997;36(1):19–28. [PubMed]
170. Herfs M, Herman L, Hubert P, et al. High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigen-presenting cells. Cancer Immunology, Immunotherapy. 2009;58(4):603–614. [PubMed]
171. Lee JJ, Takei M, Hori S, et al. The role of PGE2 in the differentiation of dendritic cells: how do dendritic cells influence T-cell polarization and chemokine receptor expression? Stem Cells. 2002;20(5):448–459. [PubMed]
172. Kaliński P, Hilkens CMU, Snijders A, Snijdewint FGM, Kapsenberg ML. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E, promote type 2 cytokine production in maturing human naive T helper cells. Journal of Immunology. 1997;159(1):28–35. [PubMed]
173. Kaliński P, Hilkens CMU, Snijders A, Snijdewint FGM, Kapsenberg ML. Dendritic cells, obtained from peripheral blood precursors in the presence of PGE2, promote Th2 responses. Advances in Experimental Medicine and Biology. 1997;417:363–367. [PubMed]
174. Sombroek CC, Stam AGM, Masterson AJ, et al. Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. Journal of Immunology. 2002;168(9):4333–4343. [PubMed]
175. Nencioni A, Lauber K, Grünebach F, et al. Cyclopentenone prostaglandins induce caspase activation and apoptosis in dendritic cells by a PPAR-γ-independent mechanism: regulation by inflammatory and T cell-derived stimuli. Experimental Hematology. 2002;30(9):1020–1028. [PubMed]
176. Katoh N, Soga F, Nara T, et al. Effect of serotonin on the differentiation of human monocytes into dendritic cells. Clinical and Experimental Immunology. 2006;146(2):354–361. [PubMed]
177. Radvanyi LG, Banerjee A, Weir M, Messner H. Low levels of interferon-α induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells. Scandinavian Journal of Immunology. 1999;50(5):499–509. [PubMed]
178. Pogue SL, Preston BT, Stalder J, Bebbington CR, Cardarelli PM. The receptor for type I IFNs is highly expressed on peripheral blood B cells and monocytes and mediates a distinct profile of differentiation and activation of these cells. Journal of Interferon and Cytokine Research. 2004;24(2):131–139. [PubMed]
179. Merad M, Angevin E, Wolfers J, et al. Generation of monocyte-derived dendritic cells from patients with renal cell cancer: modulation of their functional properties after therapy with biological response modifiers (IFN-α plus IL-2 and IL-12) Journal of Immunotherapy. 2000;23(3):369–378. [PubMed]
180. Huang YM, Adikari S, Båve U, Sanna A, Alm G. Multiple sclerosis: Interferon-beta induces CD123+BDCA2 dendritic cells that produce IL-6 and IL-10 and have no enhanced type I interferon production. Journal of Neuroimmunology. 2005;158(1-2):204–212. [PubMed]
181. Zang YCQ, Skinner SM, Robinson RR, et al. Regulation of differentiation and functional properties of monocytes and monocyte-derived dendritic cells by interferon beta in multiple sclerosis. Multiple Sclerosis. 2004;10(5):499–506. [PubMed]
182. Bartholomé EJ, Willems F, Crusiaux A, Thielemans K, Schandene L, Goldman M. IFN-β interferes with the differentiation of dendritic cells from peripheral blood mononuclear cells: selective inhibition of CD40-dependent interleukin-12 secretion. Journal of Interferon and Cytokine Research. 1999;19(5):471–478. [PubMed]
183. Hussein Y, Sanna A, Söderström M, Link H, Huang Y-M. Multiple sclerosis: expression of CDIa and production of IL-12 p70 and IFN-γ by blood mononuclear cells in patients on combination therapy with IFN-β and glatiramer acetate compared to monotherapy with IFN-β Multiple Sclerosis. 2004;10(1):16–25. [PubMed]
184. McRae BL, Nagai T, Semnani RT, Van Seventer JM, Van Seventer GA. Interferon-α and -β inhibit the in vitro differentiation of immunocompetent human dendritic cells from CD14 precursors. Blood. 2000;96(1):210–217. [PubMed]
185. Hussien Y, Sanna A, Söderström M, Link H, Huang YM. Glatiramer acetate and IFN-β act on dendritic cells in multiple sclerosis. Journal of Neuroimmunology. 2001;121(1-2):102–110. [PubMed]
186. Rongcun Y, Maes H, Corsi M, Dellner F, Wen T, Kiessling R. Interferon γ impairs the ability of monocyte-derived dendritic cells to present tumour-specific and allo-specific antigens and reduces their expression of CD1a, CD80 and CD4. Cytokine. 1998;10(10):747–755. [PubMed]
187. Delneste Y, Charbonnier P, Herbault N, et al. Interferon- switches monocyte differentiation from dendritic cells to macrophages. Blood. 2003;101(1):143–150. [PubMed]
188. Makino M, Maeda Y, Mukai T, Kaufmann SHE. Impaired maturation and function of dendritic cells by mycobacteria through IL-1β European Journal of Immunology. 2006;36(6):1443–1452. [PubMed]
189. Gupta N, Barhanpurkar AP, Tomar GB, et al. IL-3 inhibits human osteoclastogenesis and bone resorption through downregulation of c-Fms and diverts the cells to dendritic cell lineage. Journal of Immunology. 2010;185(4):2261–2272. [PubMed]
190. Yamamura K, Ohishi K, Katayama N, et al. Notch ligand Delta-1 differentially modulates the effects of gp130 activation on interleukin-6 receptor α-positive and -negative human hematopoietic progenitors. Cancer Science. 2007;98(10):1597–1603. [PubMed]
191. Encabo A, Solves P, Mateu E, Sepúlveda P, Carbonell-Uberos F, Miñana MD. Selective generation of different dendritic cell precursors from CD34+ cells by interleukin-6 and interleukin-3. Stem Cells. 2004;22(5):725–740. [PubMed]
192. Yu Z, Liu W, Liu D, Fan LI. The regulatory role of Hyper-IL-6 in the differentiation of myeloid and erythroid progenitors derived from human cord blood. Cellular Immunology. 2006;241(1):32–37. [PubMed]
193. Ratta M, Fagnoni F, Curti A, et al. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood. 2002;100(1):230–237. [PubMed]
194. Chomarat P, Banchereau J, Davoust J, Palucka AK. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nature Immunology. 2000;1(6):510–514. [PubMed]
195. Asadullah K, Friedrich M, Hanneken S, et al. Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histologic, immunohistologic, and molecular biology findings. Journal of Investigative Dermatology. 2001;116(5):721–727. [PubMed]
196. Longoni D, Piemonti L, Bernasconi S, Mantovani A, Allavena P. Interleukin-10 increases mannose receptor expression and endocytic activity in monocyte-derived dendritic cells. International Journal of Clinical and Laboratory Research. 1998;28(3):162–169. [PubMed]
197. Allavena P, Piemonti L, Longoni D, et al. IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. European Journal of Immunology. 1998;28(1):359–369. [PubMed]
198. Sato K, Nagayama H, Tadokoro K, Juji T, Takahashi TA. Interleukin-13 is involved in functional maturation of human peripheral blood monocyte-derived dendritic cells. Experimental Hematology. 1999;27(2):326–336. [PubMed]
199. Xia CQ, Kao KJ. Effect of CXC chemokine platelet factor 4 on differentiation and function of monocyte-derived dendritic cells. International Immunology. 2003;15(8):1007–1015. [PubMed]
200. Riedl E, Stöckl J, Majdic O, Scheinecker C, Knapp W, Strobl H. Ligation of E-cadherin on in vitro-generated immature Langerhans-type dendritic cells inhibits their maturation. Blood. 2000;96(13):4276–4284. [PubMed]
201. Lin YL, Liang YC, Chiang BL. Placental growth factor down-regulates type 1 T helper immune response by modulating the function of dendritic cells. Journal of Leukocyte Biology. 2007;82(6):1473–1480. [PubMed]
202. Miller-Graziano CL, De A, Laudanski K, Herrmann T, Bandyopadhyay S. HSP27: an anti-inflammatory and immunomodulatory stress protein acting to dampen immune function. Novartis Foundation Symposium. 2008;291:196–208. [PubMed]
203. Laudanski K, De A, Miller-Graziano C. Exogenous heat shock protein 27 uniquely blocks differentiation of monocytes to dendritic cells. European Journal of Immunology. 2007;37(10):2812–2824. [PubMed]
204. Laborde EA, Vanzulli S, Beigier-Bompadre M, et al. Immune complexes inhibit differentiation, maturation, and function of human monocyte-derived dendritic cells. Journal of Immunology. 2007;179(1):673–681. [PubMed]
205. Rennalls LP, Seidl T, Larkin JMG, et al. The melanocortin receptor agonist NDP-MSH impairs the allostimulatory function of dendritic cells. Immunology. 2010;129(4):610–619. [PubMed]
206. Buisson S, Triebel F. LAG-3 (CD223) reduces macrophage and dendritic cell differentiation from monocyte precursors. Immunology. 2005;114(3):369–374. [PubMed]
207. Gogolak P, Rethi B, Szatmari I, et al. Differentiation of CD1a+ and CD1a monocyte-derived dendritic cells is biased by lipid environment and PPARγ Blood. 2007;109(2):643–652. [PubMed]
208. Martino A, Volpe E, Baldini PM. The influence of lysophosphatidic acid on the immunophenotypic differentiation of human monocytes into dendritic cells. Haematologica. 2006;91(9):1273–1274. [PubMed]
209. Blüml S, Zupkovitz G, Kirchberger S, et al. Epigenetic regulation of dendritic cell differentiation and function by oxidized phospholipids. Blood. 2009;114(27):5481–5489. [PubMed]
210. Li L, Li SP, Min J, Zheng L. Hepatoma cells inhibit the differentiation and maturation of dendritic cells and increase the production of regulatory T cells. Immunology Letters. 2007;114(1):38–45. [PubMed]
211. Menetrier-Caux C, Montmain G, Dieu MC, et al. Inhibition of the differentiation of dendritic cells from CD34+ progenitors by tumor cells: role of interleukin-6 and macrophage colony- stimulating factor. Blood. 1998;92(12):4778–4791. [PubMed]
212. Motta JM, Nascimento CR, Rumjanek VM. Leukemic cell products down-regulate human dendritic cell differentiation. Cancer Immunology, Immunotherapy. 2010;59(11):1645–1653. [PubMed]
213. Gerlini G, Tun-Kyi A, Dudli C, Burg G, Pimpinelli N, Nestle FO. Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions. American Journal of Pathology. 2004;165(6):1853–1863. [PubMed]
214. Berthier-Vergnes O, Gaucherand M, Péguet-Navarro J, et al. Human melanoma cells inhibit the earliest differentiation steps of human Langerhans cell precursors but failed to affect the functional maturation of epidermal Langerhans cells. British Journal of Cancer. 2001;85(12):1944–1951. [PMC free article] [PubMed]
215. Sombroek CC, Stam AGM, Masterson AJ, et al. Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. Journal of Immunology. 2002;168(9):4333–4343. [PubMed]
216. Giordano D, Magaletti DM, Clark EA, Beavo JA. Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209) intermediate cell and impair differentiation into dendritic cells. Journal of Immunology. 2003;171(12):6421–6430. [PubMed]
217. Leslie DS, Dascher CC, Cembrola K, et al. Serum lipids regulate dendritic cell CD1 expression and function. Immunology. 2008;125(3):289–301. [PubMed]
218. Jakobsen MA, Møller BK, Lillevang ST. Serum concentration of the growth medium markedly affects monocyte-derived dendritic cells’ phenotype, cytokine production profile and capacities to stimulate in MLR. Scandinavian Journal of Immunology. 2004;60(6):584–591. [PubMed]
219. Loudovaris M, Hansen M, Suen Y, Lee SM, Casing P, Bender JG. Differential effects of autologous serum on CD34+ or monocyte-derived dendritic cells. Journal of Hematotherapy and Stem Cell Research. 2001;10(4):569–578. [PubMed]
220. Smed-Sörensen A, Moll M, Cheng TY, et al. IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via RrγRIIa. Blood. 2008;111(10):5037–5046. [PubMed]
221. Ohkuma K, Sasaki T, Kamei S, et al. Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients. Clinical and Experimental Immunology. 2007;150(3):397–406. [PubMed]
222. Xie J, Wang Y, Freeman ME, III, Barlogie B, Yi Q. β-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. Blood. 2003;101(10):4005–4012. [PubMed]
223. Dumay O, Karam A, Vian L, et al. Ultraviolet AI exposure of human skin results in Langerhans cell depletion and reduction of epidermal antigen-presenting cell function: partial protection by a broad-spectrum sunscreen. British Journal of Dermatology. 2001;144(6):1161–1168. [PubMed]
224. Hochberg M, Enk CD. Partial protection against epidermal IL-10 transcription and langerhans cell depletion by sunscreens after exposure of human skin to UVB. Photochemistry and Photobiology. 1999;70(5):766–772. [PubMed]
225. Kang K, Gilliam AC, Chen G, Tootell E, Cooper KD. In human skin, UVB initiates early induction of IL-10 over IL-12 preferentially in the expanding dermal monocytic/macrophagic population. Journal of Investigative Dermatology. 1998;111(1):31–38. [PubMed]
226. Borderie VM, Kantelip BM, Genin PO, Masse M, Laroche L, Delbosc BY. Modulation of HLA-DR and CD1a expression on human cornea with low-dose UVB irradiation. Current Eye Research. 1996;15(6):669–679. [PubMed]
227. Mitchell P, Germain C, Fiori PL, et al. Chronic exposure to Helicobacter pylori impairs dendritic cell function and inhibits Th1 development. Infection and Immunity. 2007;75(2):810–819. [PMC free article] [PubMed]
228. Krauss-Etschmann S, Gruber R, Plikat K, et al. Increase of antigen-presenting cells in the gastric mucosa of Helicobacter pylori-infected children. Helicobacter. 2005;10(3):214–222. [PubMed]
229. Michalak-Stoma A, Tabarkiewicz J, Olender A, et al. The effect of Propionibacterium acnes on maturation of dendritic cells derived from acne patients’ peripherial blood mononuclear cells. Folia Histochemica et Cytobiologica. 2008;46(4):535–539. [PubMed]
230. Correale J, Farez M. Monocyte-derived dendritic cells in multiple sclerosis: the effect of bacterial infection. Journal of Neuroimmunology. 2007;190(1-2):177–189. [PubMed]
231. Agrawal T, Vats V, Wallace PK, Salhan S, Mittal A. Role of cervical dendritic cell subsets, co-stimulatory molecules, cytokine secretion profile and beta-estradiol in development of sequalae to Chlamydia trachomatis infection. Reproductive Biology and Endocrinology. 2008;6, article no. 46 [PMC free article] [PubMed]
232. Chen X, Chang LJ. Mycoplasma-mediated alterations of in vitro generation and functions of human dendritic cells. Journal of Biomedical Science. 2005;12(1):31–46. [PubMed]
233. Amprey JL, Späth GF, Porcelli SA. Inhibition of CD1 expression in human dendritic cells during intracellular infection with Leishmania donovani. Infection and Immunity. 2004;72(1):589–592. [PMC free article] [PubMed]
234. Favali C, Tavares N, Clarêncio J, Barral A, Barral-Netto M, Brodskyn C. Leishmania amazonensis infection impairs differentiation and function of human dendritic cells. Journal of Leukocyte Biology. 2007;82(6):1401–1406. [PubMed]
235. Donovan MJ, Jayakumar A, McDowell MA. Inhibition of groups 1 and 2 CD1 molecules on human dendritic cells by Leishmania species. Parasite Immunology. 2007;29(10):515–524. [PubMed]
236. Seipel D, Ribeiro-Gomes FL, Barcelos MW, et al. Monocytes/macrophages infected with Toxoplasma gondii do not increase co-stimulatory molecules while maintaining their migratory ability. APMIS. 2009;117(9):672–680. [PubMed]
237. Fujiwara RT, Cançado GGL, Freitas PA, et al. Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals. PLoS Neglected Tropical Diseases. 2009;3(3, article e399) [PMC free article] [PubMed]
238. Riganò R, Buttari B, Profumo E, et al. Echinococcus granulosus antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response. Infection and Immunity. 2007;75(4):1667–1678. [PMC free article] [PubMed]
239. Kanan JHC, Chain BM. Modulation of dendritic cell differentiation and cytokine secretion by the hydatid cyst fluid of Echinococcus granulosus. Immunology. 2006;118(2):271–278. [PubMed]
240. Cirone M, Lucania G, Bergamo P, Trivedi P, Frati L, Faggioni A. Human herpesvirus 8 (HHV-8) inhibits monocyte differentiation into dendritic cells and impairs their immunostimulatory activity. Immunology Letters. 2007;113(1):40–46. [PubMed]
241. Gredmark S, Söderberg-Nauclér C. Human cytomegalovirus inhibits differentiation of monocytes into dendritic cells with the consequence of depressed immunological functions. Journal of Virology. 2003;77(20):10943–10956. [PMC free article] [PubMed]
242. Martino A, Volpe E, Auricchio G, Colizzi V, Baldini PM. Influence of Pertussis toxin on CD1a isoform expression in human dendritic cells. Journal of Clinical Immunology. 2006;26(2):153–159. [PubMed]
243. Wang M, Mukherjee PK, Chandra J, Lattif AA, McCormick TS, Ghannoum MA. Characterization and partial purification of Candida albicans secretory IL-12 inhibitory factor. BMC Microbiology. 2008;8, article 31 [PMC free article] [PubMed]
244. Sanchez V, Hessler C, Demonfort A, Lang J, Guy B. Comparison by flow cytometry of immune changes induced in human monocyte-derived dendritic cells upon infection with dengue 2 live-attenuated vaccine or 16681 parental strain. FEMS Immunology and Medical Microbiology. 2006;46(1):113–123. [PubMed]
245. Skorokhod OA, Alessio M, Mordmüller B, Arese P, Schwarzer E. Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: a peroxisome proliferator-activated receptor-γ-mediated effect. Journal of Immunology. 2004;173(6):4066–4074. [PubMed]
246. Bueno LL, Morais CG, Soares IS, et al. Plasmodium vivax recombinant vaccine candidate AMA-1 plays an important role in adaptive immune response eliciting differentiation of dendritic cells. Vaccine. 2009;27(41):5581–5588. [PubMed]
247. Hymery N, Léon K, Carpentier FG, Jung JL, Parent-Massin D. T-2 toxin inhibits the differentiation of human monocytes into dendritic cells and macrophages. Toxicology in Vitro. 2009;23(3):509–519. [PubMed]
248. Kyu HK, Ji HH, Jin HC, Kwang HC, Hee CE. Role of staphylococcal superantigen in atopic dermatitis: influence on keratinocytes. Journal of Korean Medical Science. 2006;21(2):315–323. [PMC free article] [PubMed]
249. Xie J, Qian J, Wang S, Freeman ME, Epstein J, Yi Q. Novel and detrimental effects of lipopolysaccharide on in vitro generation of immature dendritic cells: involvement of mitogen-activated protein kinase p38. Journal of Immunology. 2003;171(9):4792–4800. [PubMed]

Articles from Clinical and Developmental Immunology are provided here courtesy of Hindawi Publishing Corporation