{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:22:31Z","timestamp":1791256951768,"version":"4.1.0"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"23","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Memory stem T cells (T\n SCM<\/jats:sub>\n ) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. The hallmarks of HIV-1 pathogenesis are CD4\n +<\/jats:sup>\n T cell depletion and abnormal cellular activation. We investigated the impact of HIV-1 infection on the T\n SCM<\/jats:sub>\n compartment, as well as any protective role these cells may have in disease progression, by characterizing this subset in a cohort of 113 subjects with various degrees of viral control on and off highly active antiretroviral therapy (HAART). We observed that the frequency of CD8\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n was decreased in all individuals with chronic, untreated HIV-1 infection and that HAART had a restorative effect on this subset. In contrast, natural controllers of HIV-1 had the highest absolute number of CD4\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n cells among all of the infected groups. The frequency of CD4\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n predicted higher CD8\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n frequencies, consistent with a role for the CD4\n +<\/jats:sup>\n subset in helping to maintain CD8\n +<\/jats:sup>\n memory T cells. In addition, T\n SCM<\/jats:sub>\n appeared to be progenitors for effector T cells (T\n EM<\/jats:sub>\n ), as these two compartments were inversely correlated. Increased frequencies of CD8\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n predicted lower viral loads, higher CD4\n +<\/jats:sup>\n counts, and less CD8\n +<\/jats:sup>\n T cell activation. Finally, we found that T\n SCM<\/jats:sub>\n express the mucosal homing integrin \u03b14\u03b27 and can be identified in gut-associated lymphoid tissue (GALT). The frequency of mucosal CD4\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n was inversely correlated with that in the blood, potentially reflecting the ability of these self-renewing cells to migrate to a crucial site of ongoing viral replication and CD4\n +<\/jats:sup>\n T cell depletion.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n HIV-1 infection leads to profound impairment of the immune system. T\n SCM<\/jats:sub>\n constitute a recently identified lymphocyte subset with stem cell-like qualities, including the ability to generate other memory T cell subtypes, and are therefore likely to play an important role in controlling viral infection. We investigated the relationship between the size of the CD8\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n compartment and HIV-1 disease progression in a cohort of chronically infected individuals. Our results suggest that HAART restores a normal frequency of CD8\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n and that the natural preservation of this subset in the setting of untreated HIV-1 infection is associated with improved viral control and immunity. Therefore, the CD8\n +<\/jats:sup>\n T\n SCM<\/jats:sub>\n population may represent a correlate of protection in chronic HIV-1 infection that is directly relevant to the design of T cell-based vaccines, adoptive immunotherapy approaches, or the pharmacologic induction of T\n SCM<\/jats:sub>\n .\n <\/jats:p>","DOI":"10.1128\/jvi.01948-14","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T01:56:18Z","timestamp":1411610178000},"page":"13836-13844","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["The CD8\n +<\/sup>\n Memory Stem T Cell (T\n SCM<\/sub>\n ) Subset Is Associated with Improved Prognosis in Chronic HIV-1 Infection"],"prefix":"10.1128","volume":"88","author":[{"given":"Susan P.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Immunology and Allergy-LIM60, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo, Brazil"},{"name":"Institute of Investigation in Immunology\u2014iii-INCT, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Milush","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edecio","family":"Cunha-Neto","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Allergy-LIM60, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo, Brazil"},{"name":"Institute of Investigation in Immunology\u2014iii-INCT, S\u00e3o Paulo, Brazil"},{"name":"Laboratory of Immunology, Heart Institute, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esper G.","family":"Kallas","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Allergy-LIM60, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo, Brazil"},{"name":"Institute of Investigation in Immunology\u2014iii-INCT, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Kalil","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Allergy-LIM60, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo, Brazil"},{"name":"Institute of Investigation in Immunology\u2014iii-INCT, S\u00e3o Paulo, Brazil"},{"name":"Laboratory of Immunology, Heart Institute, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo, Brazil"},{"name":"Butantan Institute, Butant\u00e3, S\u00e3o Paulo\u2014SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma","family":"Somsouk","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Hunt","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Division, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Division, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F.","family":"Nixon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devi","family":"SenGupta","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, 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