gamma delta T-cell subsets in HIV controllers: potential role of T gamma delta 17 cells in the regulation of chronic immune activation

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, gamma delta T lymphocytes remain largely uncharacterized. The aim of this study was to analyse phenotypic and functional characteristics of gamma delta 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 gamma delta T cells were analysed by flow cytometry. Results: Despite normal frequencies of total gamma delta T cells, the V delta 2(+)/V delta 2(neg.) ratio was significantly reduced in HIC, albeit to a lesser extent than UT-CHI patients. Of note, nine HICs showed elevated V delta 2(neg) gamma delta T cells, as patients with UT-CHI, which was associated with higher CD8(+) T-cell activation. Interleukin (IL)-17-production by gamma delta T cells (T gamma delta 17) was better preserved in HIC than in UT-CHI patients. Proportion of total gamma delta T cells positively correlated with CD8(+) T-cell activation and HIV-DNA, IP-10 and sCD14 levels. Conversely, T gamma delta 17 cells negatively correlated with CD8(+) T- cell activation and plasma sCD14 levels. Moreover, transforming growth factor (TGF)-beta producing V delta 2(+) T cells were as dramatically depleted in HIC as in UT-CHI patients. Conclusion: The relative preservation of IL-17-producing gamma delta T cells in HIC and their negative association with immune activation raise the hypothesis that T gamma delta 17 cells potentially through prevention of microbial translocation - may participate in the control of chronic systemic immune activation. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.