{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:14:39Z","timestamp":1787026479976,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The antigen-independent, strong proliferative responses of naive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells have been well demonstrated in a particular strain of mice lacking IL-2 receptors. This type of proliferation is mainly driven by common gamma-chain (\u03b3\n                    <jats:sub>c<\/jats:sub>\n                    ) cytokines, such as IL-2, IL-7, and IL-15, present at abnormally high levels in these mice. Similarly, in the present study, we showed that mice lacking Janus kinase 3 (Jak3), a tyrosine kinase crucial for \u03b3\n                    <jats:sub>c<\/jats:sub>\n                    cytokine signaling, could induce strong proliferation of adoptively transferred naive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. This proliferation was also independent of antigenic stimulation, but heavily dependent on IL-2, as evidenced by the failure of proliferation of adoptively transferred IL-2 receptor alpha- and beta-chain-deficient naive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Consistent with this,\n                    <jats:italic>Jak3<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice showed elevated serum levels of IL-2 compared to wild-type mice, and interestingly, IL-2 production was due to high levels of accumulation of activated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in\n                    <jats:italic>Jak3<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice along with defective CD4\n                    <jats:sup>+<\/jats:sup>\n                    T regulatory cells. Collectively, these findings reveal previously unidentified unique immune contexts of\n                    <jats:italic>Jak3<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice that cause robust IL-2-driven T cell expansion and have a clinical implication for designing a treatment strategy for human patients with loss-of-function genetic mutations of\n                    <jats:italic>Jak3<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2020.616898","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:47:26Z","timestamp":1611794846000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Supraphysiological Levels of IL-2 in Jak3-Deficient Mice Promote Strong Proliferative Responses of Adoptively Transferred Naive CD8+ T Cells"],"prefix":"10.3389","volume":"11","author":[{"given":"Gil-Woo","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Woo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Jun","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Ok","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol-Heui","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Ho","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0168-9525(00)89000-9","article-title":"Jaks 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