Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Institutions: George Washington University, University of North Carolina at Chapel Hill, Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, UNC Lineberger Comprehensive Cancer Center, Frederick National Laboratory for Cancer Research, National Cancer Institute
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, George Washington University, European Commission, Ministerio de Economía y Competitividad, National Institutes of Health, Center for AIDS Research, University of Washington, Consejo Superior de Investigaciones Científicas, Instituto de Salud Carlos III, European Regional Development Fund, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: G124633989, G1561614896, Allogeneic cytotoxic gammadelta T cells for HIV cure immunotherapy, Análisis de la calidad del reservorio del VIH-1 en controladores de élite persistentes y en personas bajo cART a largo plazo, asociación con parámetros inmunitarios., G2666009886, Collaboratory of AIDS Researchers for Eradication (CARE), G3630622684, G3663452367, G4258602497, G4358663474, Análisis del perfil metabólico asociado con la progresión y con el control espontáneo de la infección por VIH. Papel de las pDCs en la reducción del tamaño del reservorio celular latente., G5091436655, Peripheral and tissue-resident gamm/delta T cells in HIV latency, G5577749326, G585697667, G6012682559, G615155586, G6176562863, G6586041785, G7131710740, G7660416320, G8422249695, G8882569155, District of Columbia Center for AIDS Research, Cancer Center Support Grant
OpenAlex ID: W4411882175