Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection
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 g...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57260-4 |
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| author | 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 Natalia Soriano-Sarabia |
| author_facet | 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 Natalia Soriano-Sarabia |
| author_sort | Brendan T. Mann |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-506bc3f7f25a4a00847fff22509fa05d |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-506bc3f7f25a4a00847fff22509fa05d2025-08-20T03:45:31ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-57260-4Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infectionBrendan T. Mann0Marta Sanz1Matthew L. Clohosey2Kayley Langlands3Alisha Chitrakar4Carles Moreno-Soriano5Joana Vitalle6Marie Anne Iannone7Ezequiel Ruiz-Mateos8Claire Deleage9Marc Siegel10Natalia Soriano-Sarabia11Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington UniversityDepartment of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington UniversityUNC-HIV Cure Center, Department of Medicine, University of North Carolina at Chapel HillDivision of Infectious Diseases, School of Medicine and Health Sciences. George Washington UniversityDepartment of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington UniversityDepartment of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington UniversityInstitute 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 ParasitologyLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillInstitute 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 ParasitologyAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, National Cancer InstituteDivision of Infectious Diseases, School of Medicine and Health Sciences. George Washington UniversityDepartment of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington UniversityAbstract 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.https://doi.org/10.1038/s41467-025-57260-4 |
| spellingShingle | 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 Natalia Soriano-Sarabia Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection Nature Communications |
| title | Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection |
| title_full | Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection |
| title_fullStr | Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection |
| title_full_unstemmed | Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection |
| title_short | Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection |
| title_sort | dual role of circulating and mucosal vδ1 t cells in the control of and contribution to persistent hiv 1 infection |
| url | https://doi.org/10.1038/s41467-025-57260-4 |
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