HIV antigens can induce TGF-β₁-producing immunoregulatory CD8⁺ T cells

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.