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.
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.
Despite normal frequencies of total γδ T cells, the Vδ2+/Vδ2neg ratio was significantly reduced in HIC, albeit to a lesser extent than UT-CHI patients. Of note, nine HICs showed elevated Vδ2neg 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.
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.
aInstitut Pasteur, Unité Régulation des Infections Rétrovirales
bINSERM U976, Laboratory of Human Immunology, Pathophysiology and Immunotherapy, Hôpital Saint-Louis, Université Paris Diderot
cInstitut Pasteur, Unité Cytokines et Inflammation
dAP-HP, Hôpital Européen Georges Pompidou
eAP-HP, Hôpital Saint-Antoine
fCentre Médical de l’Institut Pasteur, Centre d’Infectiologie Necker Pasteur
gUniversité Paris Descartes, Sorbonne Paris Cité, Paris, France.
Correspondence to Professor Laurence Weiss, AP-HP, Hôpital Européen Georges Pompidou, 75015, Paris, France. E-mail: email@example.com
Received 30 October, 2018
Revised 23 January, 2019
Accepted 5 February, 2019
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