{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:47:11Z","timestamp":1790801231835,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of na\u00efve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells.<\/jats:p>","DOI":"10.3390\/ijms25115937","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T10:42:34Z","timestamp":1717065754000},"page":"5937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7172-049X","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Benito","sequence":"first","affiliation":[{"name":"HIV and Viral Hepatitis Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Hospital Universitario Rey Juan Carlos, 28933 M\u00f3stoles, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jim\u00e9nez-Carretero","sequence":"additional","affiliation":[{"name":"Unidad de Bioinform\u00e1tica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Restrepo","sequence":"additional","affiliation":[{"name":"HIV and Viral Hepatitis Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Hospital Universitario Rey Juan Carlos, 28933 M\u00f3stoles, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Ligos","sequence":"additional","affiliation":[{"name":"Cytek Biosciences, Inc., Fremont, CA 94538, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Valent\u00edn-Quiroga","sequence":"additional","affiliation":[{"name":"Grupo de Respuesta Inmune Innata, IdiPAZ, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-6541","authenticated-orcid":false,"given":"Ignacio","family":"Mahillo","sequence":"additional","affiliation":[{"name":"Department of Statistics, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-8358","authenticated-orcid":false,"given":"Alfonso","family":"Cabello","sequence":"additional","affiliation":[{"name":"Hospital Universitario Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"L\u00f3pez-Collazo","sequence":"additional","affiliation":[{"name":"Grupo de Respuesta Inmune Innata, IdiPAZ, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"S\u00e1nchez-Cabo","sequence":"additional","affiliation":[{"name":"Unidad de Bioinform\u00e1tica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"G\u00f3rgolas","sequence":"additional","affiliation":[{"name":"Hospital Universitario Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-5986","authenticated-orcid":false,"given":"Vicente","family":"Estrada","sequence":"additional","affiliation":[{"name":"Hospital Universitario Cl\u00ednico San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-247X","authenticated-orcid":false,"given":"Norma","family":"Rall\u00f3n","sequence":"additional","affiliation":[{"name":"HIV and Viral Hepatitis Research Laboratory, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Hospital Universitario Rey Juan Carlos, 28933 M\u00f3stoles, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/COH.0b013e328345a328","article-title":"Elite controllers as a model of functional cure","volume":"6","author":"Autran","year":"2011","journal-title":"Curr. 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