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

Brendan T. Mann, Marta Sanz, Matthew L. Clohosey, Kayley Langlands, Alisha Chitrakar, Carles Moreno-Soriano, Joana Vitalle, Marie Anne Iannone, Ezequiel Ruiz-Mateos, Claire Deleage, Marc Siegel and Natalia Soriano-Sarabia ()
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Brendan T. Mann: Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University
Marta Sanz: Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University
Matthew L. Clohosey: University of North Carolina at Chapel Hill
Kayley Langlands: School of Medicine and Health Sciences. George Washington University
Alisha Chitrakar: Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University
Carles Moreno-Soriano: Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University
Joana Vitalle: Microbiology and Parasitology
Marie Anne Iannone: University of North Carolina at Chapel Hill
Ezequiel Ruiz-Mateos: Microbiology and Parasitology
Claire Deleage: National Cancer Institute
Marc Siegel: School of Medicine and Health Sciences. George Washington University
Natalia Soriano-Sarabia: Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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 identify a dual role for peripheral and tissue-resident Vδ1 T cells within the gastrointestinal mucosa of virally suppressed people with HIV. Phenotypic analyses identify an increased frequency of highly differentiated, cytotoxic effector Vδ1 T cells that inhibit HIV-1 replication in vitro coinciding with increased degranulation and IFN-γ production. Conversely, we detect an enrichment of HIV-1 DNA in tissue-resident CD4 + Vδ1 T cells in situ. Despite low CD4 expression, we find circulating Vδ1 T cells also contain HIV-1 DNA which is replication-competent. We show that T cell receptor-mediated activation of peripheral Vδ1 T cells induces 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 contribution to tissue reservoirs.

Date: 2025
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DOI: 10.1038/s41467-025-57260-4

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