{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T14:40:10Z","timestamp":1782571210824,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Innate CD8 T cells are proinflammatory effector T cells that achieve functional maturation in the thymus prior to their export into and maturation in peripheral tissues. Innate CD8 T cells produce the Th1 cytokine IFN\u03b3 but depend on the Th2 cytokine IL-4 for their generation. Thus, innate CD8 T cells can permute the intrathymic cytokine milieu by consuming a Th2 cytokine but driving a Th1 cytokine response. The cellular source of IL-4 is the NKT2 subset of invariant NKT (iNKT) cells. Consequently, NKT2 deficiency results in the lack of innate CD8 T cells. Whether NKT2 is the only iNKT subset and whether IL-4 is the only cytokine required for innate CD8 T cell generation, however, remains unclear. Here, we employed a mouse model of NKT1 deficiency, which is achieved by overexpression of the cytokine receptor IL-2R\u03b2, and assessed the role of other iNKT subsets and cytokines in innate CD8 T cell differentiation. Because IL-2R\u03b2-transgenic mice failed to generate both NKT1 and innate CD8 T cells, we postulated an in vivo requirement for IFN\u03b3-producing NKT1 cells for innate CD8 T cell development. In-depth analyses of IL-2R\u03b2-transgenic mice and IFN\u03b3-deficient mice, however, demonstrated that neither NKT1 nor IFN\u03b3 was required to induce Eomes or to drive innate CD8 T cell generation. Instead, in vivo administration of recombinant IL-4 sufficed to restore the development of innate CD8 T cells in NKT1-deficient mice, affirming that intrathymic IL-4, and not IFN\u03b3, is the limiting factor and key regulator of innate CD8 T cell generation in the thymus.<\/jats:p>","DOI":"10.3390\/cells12202433","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:11:01Z","timestamp":1696990261000},"page":"2433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proinflammatory IFN\u03b3 Is Produced by but Not Required for the Generation of Eomes+ Thymic Innate CD8 T Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Hee Yeun","family":"Won","sequence":"first","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2910-1070","authenticated-orcid":false,"given":"Nurcin","family":"Liman","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Li","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9547-9055","authenticated-orcid":false,"given":"Jung-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jameson, S.C. 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