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HLA-G+ HIV-1-specific CD8+ T cells are associated with HIV-1 immune control

Objective(s): To assess the frequency and function of HIV-1-specific HLA-G+ (histocompatibility antigen class I, G) CD8+ T cells in HIV-1 controllers and progressors. Design: We performed an observational cross-sectional cohort analysis in untreated (n = 47) and treated (n = 17) HIV-1 patients with different rates of disease progression and n = 14 healthy individuals. Methods: We evaluated the frequency, the proportion and the function of total and virus-specific HLA-G+ CD8+ T cells by tetramer or intracellular cytokine staining, followed by flow cytometric analysis. Cytokine secretion of sorted CD8+ T-cell subsets was evaluated by Luminex assays. Results: The proportion and the absolute frequency of HLA-G+ HIV-1-specific CD8+ T cells were directly associated with CD4+ T-cell counts and inversely correlated with viral loads, whereas total or HLA-G-negative HIV-1-specific CD8+ T cells were not. In functional assays, HLA-G+ CD8+ T cells from HIV-1-negative individuals had higher abilities to produce the antiviral (C-C chemokine receptor type 5) ligands MIP-1&bgr; (macrophage inflammatory protein-1ß), MIP-1&agr; and Rantes. Conclusion: HLA-G+ HIV-1-specific CD8+ T cells may represent a previously unrecognized correlate of HIV-1 immune control.