HIV-Specific TGF-β-Positive CD4⁺T Cells Do Not Express Regulatory Surface Markers and Are Regulated by CTLA-4

Abstract

CD4þ T cell dysfunction in HIV-1 infection is associated with increased CTLA-4 and TGF-b expression. In this study we described a population of TGF-b-positive CD4 þ T cells with multiple HIV specificities. These HIVspecific TGF-b-positive CD4 þ T cells did not display the immunophenotypic patterns traditionally attributed to regulatory CD4 þ T cells. TGF-b-positive CD4 þ T cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. We also examined one potential mechanism for regulating TGF-b expression by HIV-specific CD4 þ T cells. Blocking of the TGF-b receptor II led to increased HIV-specific IFNg-positive CD4þ and CD8 þ T cell responses. Interestingly, HIV-specific TGF-b-positive CD4 þ T cells did not substantially express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-b-positive CD4 þ T cell responses, and a concomitant increase in HIV-specific IFN-g-positive CD4 þ T cell responses. Our study proposes a mechanism by which HIV-specific TGF-b production may be regulated by CTLA-4 engagement.

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