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

Abstract : OBJECTIVES: HIV controllers (HICs) are rare HIV-infected individuals able to maintain undetectable viremia in the absence of antiretroviral treatment. Although HIV-specific cytotoxic T cells have been well deciphered in HIC, γδ T lymphocytes remain largely uncharacterized. The aim of this study was to analyse phenotypic and functional characteristics of γδ T cells and their relationship with immune activation, which remains abnormally elevated and associated with comorbidities in HICs. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 16 HICs, 16 patients with untreated chronic HIV infection (UT-CHI) and 20 healthy donors. Surface marker expression and cytokine production by γδ T cells were analysed 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 than UT-CHI patients. Of note, nine HICs showed elevated Vδ2 γδ T cells, as patients with UT-CHI, which was associated with higher CD8 T-cell activation. Interleukin (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. Moreover, transforming growth factor (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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Submitted on : Thursday, September 19, 2019 - 6:59:13 PM
Last modification on : Wednesday, August 19, 2020 - 11:58:42 AM

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Mathieu Chevalier, Nupur Bhatnagar, Céline Didier, Moises Lopez-Gonzalez, Juliette Pavie, et al.. γδ T-cell subsets in HIV controllers: potential role of Tγδ17 cells in the regulation of chronic immune activation. AIDS, Lippincott, Williams & Wilkins, 2019, 33 (8), pp.1283-1292. ⟨10.1097/QAD.0000000000002196⟩. ⟨pasteur-02292431⟩

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