Elrefaei, MohamedBurke, Candace M.Baker, Chris A. R.Jones, Norman G.Bousheri, StephanieBangsberg, David R.Cao, Huyen2013-01-222009Elrefaei, Mohamed, Candace M. Burke, Chris A. R. Baker, Norman G. Jones, Stephanie Bousheri, David R. Bangsberg, and Huyen Cao. 2009. TGF-\(\beta\) and IL-10 production by HIV-specific CD8+ T cells is regulated by CTLA-4 signaling on CD4+ T cells. PLoS ONE 4(12): e8194.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10206252Immune dysregulation in HIV-1 infection is associated with increased expression of inhibitory molecules such as CTLA-4, TGF-\(\beta\), and IL-10. In this study we examined one potential mechanism for regulating TGF-\(\beta\) and IL-10 expression by HIV-specific suppressor CD8+ T cells. No overlap between TGF-\(\beta\), IL-10, and IFN-\(\gamma\) cytokine production by HIV-specific CD8+ T cells was observed. TGF-\(\beta\) positive and IL-10 positive cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. TGF-\(\beta\) and IL-10 positive CD8+ T cells did not express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-\(\beta\) positive and IL-10 positive CD8+ T cell responses, and a concomitant increase in HIV-specific IFN-\(\gamma\) positive CD8+ T cell responses. Depletion of CD4+ T cells abrogated the impact of CTLA-4 on HIV-specific TGF-\(\beta\) positive and IL-10 positive CD8+ T cells. Our study suggests that CTLA-4 Signaling on CD4+ T cells regulates the inhibitory functions of the HIV-specific suppressor CD8+ T cells.en-USimmunologyimmune responseimmunity to infectionsinfectious diseasesHIV infection and AIDSJournal Article2013-01-2210.1371/journal.pone.0008194