{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T06:58:33Z","timestamp":1778309913484,"version":"3.51.4"},"reference-count":35,"publisher":"Proceedings of the National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,11,20]]},"abstract":"<jats:p>In chronic viral infections of humans and experimental animals, virus-specific CD4<jats:sup>+<\/jats:sup>T cell function is believed to be critical for induction and maintenance of host immunity that mediates effective restriction of viral replication. Because<jats:italic>in vitro<\/jats:italic>proliferation of HIV-specific memory CD4<jats:sup>+<\/jats:sup>T cells is only rarely demonstrable in HIV-infected individuals, it is presumed that HIV-specific CD4<jats:sup>+<\/jats:sup>T cells are killed upon encountering the virus, and maintenance of CD4<jats:sup>+<\/jats:sup>T cell responses in some patients causes the restriction of virus replication. In this study, proliferative responses were absent in patients with poorly restricted virus replication although HIV-specific CD4<jats:sup>+<\/jats:sup>T cells capable of producing IFN-\u03b3 were detected. In a separate cohort, interruption of antiretroviral therapy resulted in the rapid and complete abrogation of virus-specific proliferation although HIV-1-specific CD4<jats:sup>+<\/jats:sup>T cells were present. HIV-specific proliferation returned when therapy was resumed and virus replication was controlled. Further, HIV-specific CD4<jats:sup>+<\/jats:sup>T cells of viremic patients could be induced to proliferate in response to HIV antigens when costimulation was provided by anti-CD28 antibody<jats:italic>in vitro<\/jats:italic>. Thus, HIV-1-specific CD4<jats:sup>+<\/jats:sup>T cells persist but remain poorly responsive (produce IFN-\u03b3 but do not proliferate) in viremic patients. Unrestricted virus replication causes diminished proliferation of virus-specific CD4<jats:sup>+<\/jats:sup>T cells. Suppression of proliferation of HIV-specific CD4<jats:sup>+<\/jats:sup>T cells in the context of high levels of antigen may be a mechanism by which HIV or other persistently replicating viruses limit the precursor frequency of virus-specific CD4<jats:sup>+<\/jats:sup>T cells and disrupt the development of effective virus-specific immune responses.<\/jats:p>","DOI":"10.1073\/pnas.251539598","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:35:07Z","timestamp":1027694107000},"page":"13878-13883","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":155,"title":["High-level HIV-1 viremia suppresses viral antigen-specific CD4<sup>+<\/sup>T cell proliferation"],"prefix":"10.1073","volume":"98","author":[{"given":"Andrew C.","family":"McNeil","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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