{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:48:39Z","timestamp":1791294519857,"version":"4.1.0"},"reference-count":34,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,1,3]]},"abstract":"<jats:p>Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor \u03b3 chain (\u03b3c), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-\u03b3 production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R\u2212\/\u2212 mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15.<\/jats:p>","DOI":"10.1084\/jem.20041057","type":"journal-article","created":{"date-parts":[[2005,1,3]],"date-time":"2005-01-03T19:43:05Z","timestamp":1104781385000},"page":"139-148","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":646,"title":["Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function"],"prefix":"10.1084","volume":"201","author":[{"given":"Rong","family":"Zeng","sequence":"first","affiliation":[{"name":"1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanne","family":"Spolski","sequence":"additional","affiliation":[{"name":"1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"2Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SangKon","family":"Oh","sequence":"additional","affiliation":[{"name":"3Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panu E.","family":"Kovanen","sequence":"additional","affiliation":[{"name":"1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian S.","family":"Hinrichs","sequence":"additional","affiliation":[{"name":"2Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Pise-Masison","sequence":"additional","affiliation":[{"name":"4Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Radonovich","sequence":"additional","affiliation":[{"name":"4Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Brady","sequence":"additional","affiliation":[{"name":"4Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Restifo","sequence":"additional","affiliation":[{"name":"2Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay A.","family":"Berzofsky","sequence":"additional","affiliation":[{"name":"3Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren J.","family":"Leonard","sequence":"additional","affiliation":[{"name":"1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,1,3]]},"reference":[{"key":"2023072512474030200_BIB1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0092-8674(93)90167-O","volume":"73","year":"1993","journal-title":"Cell."},{"key":"2023072512474030200_BIB2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/35105066","volume":"1","year":"2001","journal-title":"Nat. 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