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1.  Regulatory T Cell Expansion and Immune Activation during Untreated HIV Type 1 Infection Are Associated with Disease Progression 
Abstract
Regulatory T cells (Tregs) may play an important role in the immunopathology of chronic HIV-1 infection due to their potent suppressive activity of both T cell activation and effector function. To investigate the correlation between Tregs and immune activation during untreated chronic HIV-1 infection, we conducted a nested case–control study within the Multicenter AIDS Cohort Study (MACS). Twenty HIV-1-infected fast progressors (FP) and 40 slow progressors (SP) were included in our study using risk-set sampling. Nine age-matched HIV-1-uninfected men (UI) were also included. Cryopreserved peripheral blood mononuclear cells (PMBCs) were tested using flow cytometry analyses. We identified Tregs as Foxp3+CD25+CD4+ T cells and assessed the activation of CD4+ and CD8+ T cells by the expression of CD38, HLADR, or both markers simultaneously. There is a relative expansion of Tregs during HIV-1 infection, which is associated with disease progression. The increased CD38 expression on both CD4+ and CD8+ T cells expressed as either percentage or median fluorescence intensity (MFI) and the elevated proportion of CD8+ T cells that is HLADR+CD38+ were all associated with rapid HIV-1 progression. Counter to the assumed role of Tregs as the suppressors of activation, the expansion of Tregs was positively correlated with CD4+ T cell activation among HIV-1-infected fast progressors. The high level of Tregs associated with rapid HIV progression may suggest a detrimental role of these cells in the immune control of HIV-1 infection.
doi:10.1089/aid.2008.0140
PMCID: PMC2782619  PMID: 19239357
2.  Recreational Drug Use and Risk of Kaposi's Sarcoma in HIV- and HHV-8-Coinfected Homosexual Men 
Abstract
Experimental data suggested that exposure to recreational drugs might adversely affect antitumor immunity, which led us to examine the hypothesis that use of marijuana, cocaine, poppers, and amphetamines might increase the risk of Kaposi's Sarcoma (KS) in HIV- and HHV-8-coinfected homosexual men. We analyzed data prospectively collected from the Multicenter AIDS Cohort Study (MACS) between 1984 and 2002. Among the 1335 HIV- and HHV-8-coinfected white men, 401 KS cases were identified. Multivariable Cox regression models were used to estimate the effects of time-varying recreational drug use on KS risk adjusting for potential confounders. The effects of both recent use (6 months prior) of recreational drugs and lagged exposure (i.e., use from 3 and 5 years prior) were examined. We did not observe any clear association with KS for recent use of any of the four drugs. In the analyses using lagged exposures, KS risk was associated with use of poppers 3–5 years prior [hazard ratio (HR)3 years prior = 1.27, 95% CI (0.97–1.67), HR5 years prior = 1.46 (1.01–2.13)]. However, no clear dose-response relationship was observed. These findings do not support a biological association between use of these substances and KS development in HIV- and HHV-8-coinfected homosexual men.
doi:10.1089/aid.2008.0196
PMCID: PMC2981355  PMID: 19108691
3.  Regulatory T Cell Expansion and Immune Activation during Untreated HIV Type 1 Infection Are Associated with Disease Progression 
Regulatory T cells (Tregs) may play an important role in the immunopathology of chronic HIV-1 infection due to their potent suppressive activity of both T cell activation and effector function. To investigate the correlation between Tregs and immune activation during untreated chronic HIV-1 infection, we conducted a nested case–control study within the Multicenter AIDS Cohort Study (MACS). Twenty HIV-1-infected fast progressors (FP) and 40 slow progressors (SP) were included in our study using risk-set sampling. Nine age-matched HIV-1-uninfected men (UI) were also included. Cryopreserved peripheral blood mononuclear cells (PMBCs) were tested using flow cytometry analyses. We identified Tregs as Foxp3+CD25+CD4+ T cells and assessed the activation of CD4+ and CD8+ T cells by the expression of CD38, HLADR, or both markers simultaneously. There is a relative expansion of Tregs during HIV-1 infection, which is associated with disease progression. The increased CD38 expression on both CD4+ and CD8+ T cells expressed as either percentage or median fluorescence intensity (MFI) and the elevated proportion of CD8+ T cells that is HLADR+CD38+ were all associated with rapid HIV-1 progression. Counter to the assumed role of Tregs as the suppressors of activation, the expansion of Tregs was positively correlated with CD4+ T cell activation among HIV-1-infected fast progressors. The high level of Tregs associated with rapid HIV progression may suggest a detrimental role of these cells in the immune control of HIV-1 infection.
doi:10.1089/aid.2008.0140
PMCID: PMC2782619  PMID: 19239357

Results 1-3 (3)