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γδ T-cell subsets in HIV controllers: potential role of Tγδ17 cells in the regulation of chronic immune activation.

AIDS 2019 March 12
OBJECTIVES: HIV controllers (HIC) are rare HIV-infected individuals able to maintain undetectable viremia in the absence of antiretroviral treatment. While HIV-specific cytotoxic T cells have been well deciphered in HIC, γδ T lymphocytes remain largely uncharacterized. The aim of this study was to analyze phenotypic and functional characteristics of γδ T cells and their relationship with immune activation, which remain abnormally elevated and associated with comorbidities in HIC.

METHODS: PBMC were isolated from 16 HIC, 16 patients with untreated chronic HIV infection (UT-CHI) and 20 healthy donors (HD). Surface marker expression and cytokine production by γδ T cells were analyzed by flow cytometry.

RESULTS: Despite normal frequencies of total γδ T cells, the Vδ2/Vδ2 ratio was significantly reduced in HIC, albeit to a lesser extent compared to UT-CHI patients. Of note, 9 HIC showed elevated Vδ2 γδ T cells, as patients with UT-CHI, which was associated to higher CD8 T-cell activation. IL-17-production by γδ T cells (Tγδ17) was better preserved in HIC than in UT-CHI patients. Proportion of total γδ T cells positively correlated with CD8 T-cell activation and HIV-DNA, IP-10 and sCD14 levels. Conversely, Tγδ17 cells negatively correlated with CD8 T-cell activation and plasma sCD14 levels. Besides, TGF-β-producing Vδ2 T cells were as dramatically depleted in HIC as in UT-CHI patients.

CONCLUSION: The relative preservation of IL-17-producing γδ T cells in HIC and their negative association with immune activation raise the hypothesis that Tγδ17 cells - potentially through prevention of microbial translocation - may participate in the control of chronic systemic immune activation.

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