HIV Antigens Can Induce TGF-β1-Producing Immunoregulatory CD8+ T Cells

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Abstract
HIV-infected individuals may progressively lose both HIV-specific and unrelated CTL responses despite the high number of circulating CD8+ T cells. In this study, we report that ∼25% of HIV+ donors produced TGF-β1 in response to stimulation with HIV proteins or peptides. The production of TGF-β1 was sufficient to significantly reduce the IFN-γ response of CD8+ cells to both HIV and vaccinia virus proteins. Ab to TGF-β reversed the suppression. We found the source of the TGF-β1 to be predominantly CD8+ cells. Different peptide pools stimulated TGF-β1 and IFN-γ in the same individual. The TGF-β1 secreting cells have distinct peptide specificity from the IFN-γ producing cells. This represents an important mechanism by which an HIV-specific response can nonspecifically suppress both HIV-specific and unrelated immune responses.