Dual role of circulating and mucosal Vd1 T cells in the control of and contribution to persistent HIV-1 infection

Author:

Mann, Brendan T

Sanz, Marta

Clohosey, Matthew L

Langlands, Kayley

Chitrakar, Alisha

Moreno-Soriano, Carles

Vitalle, Joana

Iannone, Marie Anne

Ruiz-Mateos, Ezequiel

Deleage,Claire [ORCID]

Siegel, Marc [ORCID]

Soriano-Sarabia, Natalia [ORCID]
Author Address

Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University, Washington, DC, USA., UNC-HIV Cure Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Division of Infectious Diseases, School of Medicine and Health Sciences. George Washington University, Washington, DC, USA., 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., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA., Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University, Washington, DC, USA. nataliasorsar@gwu.edu.,

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 Vd1T cells within the gastrointestinal mucosa of virally suppressed people with HIV. Phenotypic analyses identify an increased frequency of highly differentiated, cytotoxic effector Vd1T cells that inhibit HIV-1 replication in vitro coinciding with increased degranulation and IFN-gamma production. Conversely, we detect an enrichment of HIV-1 DNA in tissue-resident CD4 + Vd1 T cells in situ. Despite low CD4 expression, we find circulating Vd1 T cells also contain HIV-1 DNA which is replication-competent. We show that T cell receptor-mediated activation of peripheral Vd1 T cells induces de novo upregulation of CD4 providing a plausible mechanism for increased permissibility to infection. These findings highlight juxtaposing roles for Vd1 T cells in HIV-1 persistence including contribution to tissue reservoirs. © 2025. The Author(s).

See More

Author Address