PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-2 (2)
 

Clipboard (0)
None
Journals
Authors
Year of Publication
Document Types
1.  Costimulation through B7-2 (CD86) Is Required for the Induction of a Lung Mucosal T Helper Cell 2 (TH2) Immune Response and Altered Airway Responsiveness 
The Journal of Experimental Medicine  1997;185(9):1671-1680.
The recruitment of eosinophils into the airways after allergen exposure is dependent on interleukin (IL) 5 secreted from antigen-specific CD4+ T cells of the T helper cell (Th) 2 subset. However, while it is established that costimulation through CD28 is required for TCR-mediated activation and IL-2 production, the importance of this mechanism for the induction of a Th2 immune response is less clear. In the present study, we administered the fusion protein CTLA-4 immunoglobulin (Ig) into the lungs before allergen provocation to determine whether CD28/CTLA-4 ligands are required for allergen-induced eosinophil accumulation and the production of Th2 cytokines. Administration of CTLA-4 Ig inhibited the recruitment of eosinophils into the lungs by 75% and suppressed IgE in the bronchoalveolar lavage fluid. CTLA-4 Ig also inhibited the production of IL-4, IL-5, and IL-10 by 70–80% and enhanced interferon-γ production from CD3–T cell receptor–activated lung Thy1.2+ cells. Allergen exposure upregulated expression of B7-2, but not B7-1, on B cells from the lung within 24 h. Moreover, airway administration of an anti-B7-2 monoclonal antibody (mAb) inhibited eosinophil infiltration, IgE production, and Th2 cytokine secretion comparable in magnitude to that observed with CTLA-4 Ig. Treatment with an anti-B7-1 mAb had a small, but significant effect on eosinophil accumulation, although was less effective in inhibiting Th2 cytokine production. The anti-B7-2, but not anti-B7-1, mAb also inhibited antigen-induced airway hyperresponsiveness in vivo. In all of the parameters assessed, the combination of both the anti-B7-1 and anti-B7-2 mAb was no more effective than anti-B7-2 mAb treatment alone. We propose that strategies aimed at inhibition of CD28 interactions with B7-2 molecules may represent a novel therapeutic target for the treatment of lung mucosal allergic inflammation.
PMCID: PMC2196297  PMID: 9151904
2.  Th2 cells and cytokine networks in allergic inflammation of the lung 
Mediators of Inflammation  1995;4(4):239-247.
The cytokines released from Th2 and Th2-like cells are likely to be central to the pathophysiolgy of asthma and allergy, contributing to aberrant IgE production, eosinophilia and, perhaps, mucosal susceptibility to viral infection. IL-4 has emerged as a central target, not only for B cell IgE production, but also in the commitment of both CD4+ and CD8+ T cells to cells with Th2 effector function capable of secreting IL-5 resultlng in eosinophilic inflammation. In view of the central role of this cytokine and the evidence that glucocorticoids are unable to modify many IL-4 dependent effects, Th2 inhibitors may prove to be novel therapies for the treatment of bronchial asthma.
doi:10.1155/S096293519500038X
PMCID: PMC2365650  PMID: 18475645

Results 1-2 (2)