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-1β (macrophage inflammatory protein-1ß), MIP-1α and Rantes. CONCLUSION:HLA-G HIV-1-specific CD8 T cells may represent a previously unrecognized correlate of HIV-1 immune control.