{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:12:44Z","timestamp":1791306764703,"version":"4.3.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2004,3,1]],"date-time":"2004-03-01T00:00:00Z","timestamp":1078099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>An in vitro proliferative defect has been observed in HIV-1-specific CD4+ T cells from infected subjects with high-level plasma HIV-1 viremia. To determine the mechanism of this defect, HIV-1 Gag-specific CD4+ T cells from treated and untreated HIV-1-infected subjects were analyzed for cytokine profile, proliferative capacity, and maturation state. Unexpectedly high frequencies of HIV-1-specific, IL-2-producing CD4+ T cells were measured in subjects with low or undetectable plasma HIV-1 loads, regardless of treatment status, and IL-2 frequencies correlated inversely with viral loads. IL-2-producing CD4+ T cells also primarily displayed a central memory (TCm; CCR7+CD45RA\u2212) maturation phenotype, whereas IFN-\u03b3-producing cells were mostly effector memory (TEm, CCR7\u2212CD45RA\u2212). Among Gag-specific, IFN-\u03b3-producing CD4+ T cells, higher TEm frequencies and lower TCm frequencies were observed in untreated, high viral load subjects than in subjects with low viral loads. The percentage of HIV-1 Gag-specific CD4+ TCm correlated inversely with HIV-1 viral load and directly with Gag-specific CD4+ T cell proliferation, whereas the opposite relationships were observed for HIV-1-specific CD4+ TEm. These results suggest that HIV-1 viremia skews Gag-specific CD4+ T cells away from an IL-2-producing TCm phenotype and toward a poorly proliferating TEm phenotype, which may limit the effectiveness of the HIV-1-specific immune response.<\/jats:p>","DOI":"10.4049\/jimmunol.172.5.3337","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:21:06Z","timestamp":1398036066000},"page":"3337-3347","source":"Crossref","is-referenced-by-count":85,"title":["Effects of Sustained HIV-1 Plasma Viremia on HIV-1 Gag-Specific CD4+ T Cell Maturation and Function"],"prefix":"10.1093","volume":"172","author":[{"given":"Brent E","family":"Palmer","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Colorado Health Sciences Center , Denver, CO 80262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Boritz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Health Sciences Center , Denver, CO 80262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara C","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Health Sciences Center , Denver, CO 80262"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,3,1]]},"reference":[{"key":"2026020214140326600_R1","first-page":"477","volume-title":"J. 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