{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:28:11Z","timestamp":1791062891970,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T00:00:00Z","timestamp":1344211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:p>HIV\u2010induced immune activation leads to expansion of a subset of human CD8<jats:sup>+<\/jats:sup> T cells expressing HLA\u2010DR antigens. Expansion of CD8<jats:sup>+<\/jats:sup>HLA\u2010DR<jats:sup>+<\/jats:sup> T cells can be also observed in non\u2010HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent \u201cimmune exhaustion\u201d and\/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR engagement. Detailed cell cycle analysis revealed that compared with their CD8<jats:sup>+<\/jats:sup>HLA\u2010DR<jats:sup>\u2212<\/jats:sup> counterpart, the CD8<jats:sup>+<\/jats:sup>HLA\u2010DR<jats:sup>+<\/jats:sup> T\u2010cell pool contained an increased fraction of cells in S\u2010phase with elevated levels of the G2\/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8<jats:sup>+<\/jats:sup> pool of cells in vivo that undergo further expansion independent of ongoing TCR engagement. No qualitative differences were noted between CD8<jats:sup>+<\/jats:sup>HLA\u2010DR<jats:sup>+<\/jats:sup> cells from HIV<jats:sup>+<\/jats:sup> and HIV<jats:sup>\u2212<\/jats:sup> donors, indicating that the generation of CD8<jats:sup>+<\/jats:sup>HLA\u2010DR<jats:sup>+<\/jats:sup> T cells is a part of normal immune regulation that is exaggerated in the setting of HIV\u20101 infection.<\/jats:p>","DOI":"10.1002\/eji.201142046","type":"journal-article","created":{"date-parts":[[2012,7,10]],"date-time":"2012-07-10T09:42:21Z","timestamp":1341913341000},"page":"2608-2620","source":"Crossref","is-referenced-by-count":26,"title":["The CD8<sup>+<\/sup>HLA\u2010DR<sup>+<\/sup> T cells expanded in HIV\u20101 infection are qualitatively identical to those from healthy controls"],"prefix":"10.1002","volume":"42","author":[{"given":"Hiromi","family":"Imamichi","sequence":"first","affiliation":[{"name":"Clinical and Molecular Retrovirology Section Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Lempicki","sequence":"additional","affiliation":[{"name":"Clinical Services Program Applied\/Developmental Research Directorate, SAIC\u2010Frederick, Inc. 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