{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:35:34Z","timestamp":1774038934043,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013489","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000}}],"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Agency for Research on HIV\/AIDS and Emerging Infectious Diseases","award":["ECTZ204599"],"award-info":[{"award-number":["ECTZ204599"]}]},{"name":"National Agency for Research on HIV\/AIDS and Emerging Infectious Diseases","award":["ECTZ205647"],"award-info":[{"award-number":["ECTZ205647"]}]},{"DOI":"10.13039\/100009060","name":"Sidaction","doi-asserted-by":"publisher","award":["12937"],"award-info":[{"award-number":["12937"]}],"id":[{"id":"10.13039\/100009060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>V\u03b4<jats:sub>1<\/jats:sub> \u03b3\u03b4 T cells are key players in innate and adaptive immunity, particularly at mucosal interfaces such as the gut. An increase in circulating V\u03b4<jats:sub>1<\/jats:sub> cells has long been observed in people with HIV-1, but remains poorly understood. We performed a comprehensive characterization of V\u03b4<jats:sub>1<\/jats:sub> T cells in blood and duodenal intra-epithelial lymphocytes, obtained from endoscopic mucosal biopsies of 15 people with HIV-1 on antiretroviral therapy and 15 HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137). We deciphered the phenotype, functional profile, single-cell transcriptome and repertoire of V\u03b4<jats:sub>1<\/jats:sub> cells and unraveled their relationships with the possible triggers involved, in particular CMV and microbiota. We also assessed whether V\u03b4<jats:sub>1<\/jats:sub> T cells may play a role in controlling the HIV-1 reservoir. V\u03b4<jats:sub>1<\/jats:sub> T cells were mainly terminally differentiated effectors that clonally expanded in the blood with some trafficking with the gut of people with HIV-1. Most expressed CX3CR1 and displayed a highly cytotoxic profile, but low cytokine production, supported by a transcriptomic shift towards enhanced effector lymphocytes. This expansion was associated with CMV status and markers of occult replication, but also with changes in the duodenal and blood-translocated microbiota. Cytotoxic, but not IFN-\u03b3-producing, V\u03b4<jats:sub>1<\/jats:sub> T cells were negatively associated with cell-associated HIV-1 RNA in both the blood and duodenal compartments. The increase in V\u03b41 T cells observed in people with HIV-1 has multiple triggers, particularly CMV and microbiota, and may in turn contribute to the control of the HIV-1 reservoir.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013489","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T18:05:46Z","timestamp":1757354746000},"page":"e1013489","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytotoxic CX3CR1+ V\u03b41 T cells clonally expand in an interplay of CMV, microbiota, and HIV-1 persistence in people on antiretroviral therapy"],"prefix":"10.1371","volume":"21","author":[{"given":"Nived","family":"Collercandy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Vellas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon","family":"Nayrac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Requena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Richarme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Laure","family":"Iscache","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justine","family":"Latour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Barange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Alric","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Martin-Blondel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Serino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Izopet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-3581","authenticated-orcid":true,"given":"Pierre","family":"Delobel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"issue":"6","key":"ppat.1013489.ref001","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1084\/jem.20040874","article-title":"CD4 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