{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:48:12Z","timestamp":1791920892194,"version":"4.3.4"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["142294"],"award-info":[{"award-number":["142294"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The differentiation and function of immunosuppressive regulatory T cells (Tregs) is dictated by the master transcription factor FoxP3. During HIV infection, there is an increase in Treg frequencies in the peripheral blood and lymphoid tissues. This accentuates immune dysfunction and disease progression. Expression of FoxP3 by thymic Tregs (tTregs) is partially controlled by TGF-\u03b2. This cytokine also contributes to Treg development in the peripheral blood and lymphoid tissues. Although TGF-\u03b2 mediates lymphoid tissue fibrosis and peripheral Treg differentiation in HIV-infected individuals, its role in the induction and maintenance of Tregs within the thymus during HIV infection remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thymocytes were isolated from fresh human thymic tissues obtained from pediatric patients undergoing cardiac surgery. Infection by both R5- and X4-tropic HIV-1 strains and TGF-\u03b2 treatment of human thymocytes was performed in an <jats:italic>in vitro<\/jats:italic> co-culture model with OP9-DL1 cells expressing Notch ligand delta-like 1 without T cell receptor (TCR) activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Despite high expression of CCR5 and CXCR4 by tTregs, FoxP3\u2009+\u2009 CD3<jats:sup>high<\/jats:sup>CD8- thymocytes were much less prone to <jats:italic>in vitro<\/jats:italic> infection with R5- and X4-tropic HIV strains compared to FoxP3-CD3<jats:sup>high<\/jats:sup>CD8- thymocytes. As expected, CD3<jats:sup>high<\/jats:sup>CD4+ thymocytes, when treated with TGF-\u03b21, upregulated CD127 and this treatment resulted in increased FoxP3 expression and Treg differentiation, but did not affect the rate of HIV infection. FoxP3 expression and Treg frequencies remained unchanged following <jats:italic>in vitro<\/jats:italic> HIV infection alone or in combination with TGF-\u03b21.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FoxP3 expression and tTreg differentiation is not affected by <jats:italic>in vitro<\/jats:italic> HIV infection alone or the combination of <jats:italic>in vitro<\/jats:italic> HIV infection and TGF-\u03b2 treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1217801","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T08:14:56Z","timestamp":1689927296000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of in vitro HIV infection on human thymic regulatory T cell differentiation"],"prefix":"10.3389","volume":"14","author":[{"given":"Sharada","family":"Swaminathan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Scorza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Yero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Farnos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C.","family":"Burke Schinkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Angel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad-Ali","family":"Jenabian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1128\/JVI.78.5.2454-2459.2004","article-title":"Human CD4+ CD25+regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens","volume":"78","author":"Aandahl","year":"2004","journal-title":"J. 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