{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:56:02Z","timestamp":1791064562344,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"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":[[2013,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD8+ T cells are fundamental for immune-mediated clearance of viral infections and contribute to immune pathology in autoimmune diseases such as type 1 diabetes. To execute these functions, CD8+ T cells must differentiate into CTLs, a process that is precisely regulated by a variety of cytokines, costimulatory molecules, and transcription factors. IL-21 is an IL-2 family cytokine and a growth factor for multiple lymphocyte effector lineages, including cytotoxic CD8+ T cells. Recent studies demonstrate that loss of IL-21 signaling results in reduced viral clearance in models of lymphocytic choriomeningitis virus infection, and also protection from type 1 diabetes in the NOD model. This is most likely the result of impaired CD8+ CTL function in the absence of IL-21 signaling. Currently, the mechanisms by which IL-21 promotes CTL differentiation in CD8+ T cells remain unclear, particularly the identity of the relevant transcription factor(s). We show that IL-21 promotes CTL function in vitro and killing of pancreatic islets in vivo via the use of transgenic mice expressing IL-21 in pancreatic \u03b2 cells. We demonstrate that IL-21 induces the expression of the transcription factor T-bet in CD8+ T cells, predominantly via STAT1, and that T-bet is required for the induction of cytolytic molecules, including perforin and granzyme B in response to IL-21. Finally, we show that IL-21\u2013induced CTL function is T-bet dependent, as T-bet deficiency results in defective IL-21\u2013dependent cytotoxicity in CD8+ T cells in vitro and in vivo. Thus, IL-21 drives CD8+ CTL differentiation via the actions of the transcription factor T-bet.<\/jats:p>","DOI":"10.4049\/jimmunol.1201730","type":"journal-article","created":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:17:03Z","timestamp":1363047423000},"page":"3977-3984","source":"Crossref","is-referenced-by-count":90,"title":["IL-21 Promotes CD8+ CTL Activity via the Transcription Factor T-bet"],"prefix":"10.1093","volume":"190","author":[{"given":"Andrew P R","family":"Sutherland","sequence":"first","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"},{"name":"Harvard Medical School , Boston, MA 02115"},{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Joller","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"},{"name":"Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Michaud","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue M","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"},{"name":"Harvard Medical School , Boston, MA 02115"},{"name":"Department of Immunology, Garvan Institute of Medical Research , Sydney, New South Wales 2010,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K","family":"Kuchroo","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"},{"name":"Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Grusby","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,4,15]]},"reference":[{"key":"2025032406520447800_r1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.immunol.21.120601.141114","article-title":"CD8 T cell responses to infectious pathogens","volume":"21","author":"Wong","year":"2003","journal-title":"Annu. 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