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γδ T-cell subsets in HIV controllers

potential role of Tγδ17 cells in the regulation of chronic immune activation

Chevalier, Mathieu F.a,b,†; Bhatnagar, Nupura,c,†; Didier, Célinea; Lopez-Gonzalez, Moisesa,c; Pavie, Julietted; Bollens, Dianee; Duvivier, Claudinef; Collias, Liod; Jung, Corinned; Scott-Algara, Daniela,c; Girard, Pierre-Mariee; Weiss, Laurencea,c,d,g for the ANRS EP56 group

doi: 10.1097/QAD.0000000000002196

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+/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.

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.

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:

Received 30 October, 2018

Revised 23 January, 2019

Accepted 5 February, 2019

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