Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection

Brendan T. Mann, Departments of Microbiology, Immunology and Tropical Medicine and The George Washington University, Washington, DC, USA.
Marta Sanz, Departments of Microbiology, Immunology and Tropical Medicine and The George Washington University, Washington, DC, USA.
Matthew Clohosey, Departments of UNC-HIV Cure Center, Department of Medicine and University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kayley Langlands, Departments of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Alisha Chitrakar, Departments of Microbiology, Immunology and Tropical Medicine and The George Washington University, Washington, DC, USA.
Carles Moreno, Departments of Microbiology, Immunology and Tropical Medicine and The George Washington University, Washington, DC, USA.
Joana Vitalle, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain.
Marie Anne Iannone, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ezequiel Ruiz-Mateos, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain.
Claire Deleage, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Marc Siegel, Departments of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Natalia Soriano-Sarabia, Departments of Microbiology, Immunology and Tropical Medicine and The George Washington University, Washington, DC, USA.

Document Type

Journal Article

Publication Date

8-2-2024

Journal

Research square

DOI

10.21203/rs.3.rs-4784403/v1

Abstract

Curative strategies for human immunodeficiency virus (HIV-1) infection are hindered by incomplete characterization of the latent reservoir and limited enhancement of anti-HIV immune responses. In this study, we identified a novel dual role for peripheral and tissue-resident Vδ1 T cells within the gastrointestinal mucosa of virally suppressed people with HIV. Phenotypic analyses identified an increased frequency of highly differentiated, cytotoxic effector Vδ1 T cells that exerted potent inhibition of HIV-1 replication in vitro coinciding with direct increases in cytolytic function. Conversely, we detected an enrichment of HIV-1 DNA in tissue-resident CD4+Vδ1 T cells in situ. Despite low CD4 expression, we found circulating Vδ1 T cells also contained HIV-1 DNA which was replication-competent. We show that TCR-mediated activation of peripheral Vδ1 T cells induced de novo upregulation of CD4 providing a plausible mechanism for increased permissibility to infection. These findings highlight juxtaposing roles for Vδ1 T cells in HIV-1 persistence including significant contribution to tissue reservoirs.

Department

Microbiology, Immunology, and Tropical Medicine

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