{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:30:32Z","timestamp":1770910232687,"version":"3.50.1"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,4,19]]},"abstract":"<jats:p>The T-box transcription factor T-bet is known to control lineage commitment and interferon-\u03b3 production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter\u2013lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-\u03b3, but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector\/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.<\/jats:p>","DOI":"10.1084\/jem.20031873","type":"journal-article","created":{"date-parts":[[2004,4,19]],"date-time":"2004-04-19T18:37:59Z","timestamp":1082399879000},"page":"1153-1162","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["T-bet Controls Autoaggressive CD8 Lymphocyte Responses in Type 1 Diabetes"],"prefix":"10.1084","volume":"199","author":[{"given":"Amy E.","family":"Juedes","sequence":"first","affiliation":[{"name":"1Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"1Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Togher","sequence":"additional","affiliation":[{"name":"1Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie H.","family":"Glimcher","sequence":"additional","affiliation":[{"name":"2Department of Immunology and Infectious Disease, Harvard School of Public Health and Department of Medicine, Harvard Medical School, Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias G.","family":"von Herrath","sequence":"additional","affiliation":[{"name":"1Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2004,4,19]]},"reference":[{"key":"2023072512324798000_BIB1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","volume":"100","year":"2000","journal-title":"Cell."},{"key":"2023072512324798000_BIB2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1126\/science.1065543","volume":"295","year":"2002","journal-title":"Science."},{"key":"2023072512324798000_BIB3","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1126\/science.1065544","volume":"295","year":"2002","journal-title":"Science."},{"key":"2023072512324798000_BIB4","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/nm0602-567","volume":"8","year":"2002","journal-title":"Nat. Med."},{"key":"2023072512324798000_BIB5","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1084\/jem.20011956","volume":"195","year":"2002","journal-title":"J. Exp. Med."},{"key":"2023072512324798000_BIB6","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0065-2776(02)80014-1","volume":"80","year":"2002","journal-title":"Adv. Immunol."},{"key":"2023072512324798000_BIB7","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0092-8674(91)90165-U","volume":"65","year":"1991","journal-title":"Cell."},{"key":"2023072512324798000_BIB8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0092-8674(91)90164-T","volume":"65","year":"1991","journal-title":"Cell."},{"key":"2023072512324798000_BIB9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/1074-7613(94)90101-5","volume":"1","year":"1994","journal-title":"Immunity."},{"key":"2023072512324798000_BIB10","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.4049\/jimmunol.163.10.5374","volume":"163","year":"1999","journal-title":"J. Immunol."},{"key":"2023072512324798000_BIB11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1074-7613(00)80121-1","volume":"11","year":"1999","journal-title":"Immunity."},{"key":"2023072512324798000_BIB12","doi-asserted-by":"crossref","first-page":"7023","DOI":"10.4049\/jimmunol.166.12.7023","volume":"166","year":"2001","journal-title":"J. Immunol."},{"key":"2023072512324798000_BIB13","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4049\/jimmunol.164.1.208","volume":"164","year":"2000","journal-title":"J. Immunol."},{"key":"2023072512324798000_BIB14","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.2337\/diabetes.49.11.1801","volume":"49","year":"2000","journal-title":"Diabetes."},{"key":"2023072512324798000_BIB15","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1172\/JCI6266","volume":"103","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2023072512324798000_BIB16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1074-7613(02)00338-2","volume":"17","year":"2002","journal-title":"Immunity."},{"key":"2023072512324798000_BIB17","doi-asserted-by":"crossref","first-page":"12538","DOI":"10.1073\/pnas.95.21.12538","volume":"95","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072512324798000_BIB18","doi-asserted-by":"crossref","first-page":"5945","DOI":"10.4049\/jimmunol.165.10.5945","volume":"165","year":"2000","journal-title":"J. Immunol."},{"key":"2023072512324798000_BIB19","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1084\/jem.178.2.589","volume":"178","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072512324798000_BIB20","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1099\/0022-1317-64-8-1689","volume":"64","year":"1983","journal-title":"J. Gen. Virol."},{"key":"2023072512324798000_BIB21","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/1074-7613(95)90062-4","volume":"3","year":"1995","journal-title":"Immunity."},{"key":"2023072512324798000_BIB22","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1128\/jvi.69.4.2297-2305.1995","volume":"69","year":"1995","journal-title":"J. Virol."},{"key":"2023072512324798000_BIB23","doi-asserted-by":"crossref","first-page":"3402","DOI":"10.1002\/eji.1830251230","volume":"25","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"2023072512324798000_BIB24","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1172\/JCI13296","volume":"108","year":"2001","journal-title":"J. Clin. Invest."},{"key":"2023072512324798000_BIB25","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S1074-7613(00)80540-3","volume":"8","year":"1998","journal-title":"Immunity."},{"key":"2023072512324798000_BIB26","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/342559a0","volume":"342","year":"1989","journal-title":"Nature."},{"key":"2023072512324798000_BIB27","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.2337\/diabetes.50.12.2700","volume":"50","year":"2001","journal-title":"Diabetes."},{"key":"2023072512324798000_BIB28","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.4049\/jimmunol.164.7.3689","volume":"164","year":"2000","journal-title":"J. Immunol."},{"key":"2023072512324798000_BIB29","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1098\/rstb.2000.0577","volume":"355","year":"2000","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"2023072512324798000_BIB30","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.4049\/jimmunol.157.7.3074","volume":"157","year":"1996","journal-title":"J. Immunol."},{"key":"2023072512324798000_BIB31","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1084\/jem.183.5.2129","volume":"183","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072512324798000_BIB32","doi-asserted-by":"crossref","first-page":"8056","DOI":"10.1128\/jvi.68.12.8056-8063.1994","volume":"68","year":"1994","journal-title":"J. Virol."},{"key":"2023072512324798000_BIB33","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1006\/viro.1995.1477","volume":"212","year":"1995","journal-title":"Virology."},{"key":"2023072512324798000_BIB34","doi-asserted-by":"crossref","first-page":"5565","DOI":"10.4049\/jimmunol.167.10.5565","volume":"167","year":"2001","journal-title":"J. Immunol."},{"key":"2023072512324798000_BIB35","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1128\/jvi.70.2.1072-1079.1996","volume":"70","year":"1996","journal-title":"J. Virol."},{"key":"2023072512324798000_BIB36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S1074-7613(02)00290-X","volume":"16","year":"2002","journal-title":"Immunity."},{"key":"2023072512324798000_BIB37","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1084\/jem.185.3.531","volume":"185","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072512324798000_BIB38","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nature01441","volume":"421","year":"2003","journal-title":"Nature."},{"key":"2023072512324798000_BIB39","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nm866","volume":"9","year":"2003","journal-title":"Nat. Med."},{"key":"2023072512324798000_BIB40","doi-asserted-by":"crossref","first-page":"15818","DOI":"10.1073\/pnas.2636938100","volume":"100","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072512324798000_BIB41","first-page":"225","volume":"4","year":"2003","journal-title":"Nat. Immunol."},{"key":"2023072512324798000_BIB42","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1128\/JVI.73.7.5918-5925.1999","volume":"73","year":"1999","journal-title":"J. Virol."},{"key":"2023072512324798000_BIB43","doi-asserted-by":"crossref","first-page":"7749","DOI":"10.1073\/pnas.1332767100","volume":"100","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/199\/8\/1153\/1714078\/jem19981153.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/199\/8\/1153\/1714078\/jem19981153.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T12:43:20Z","timestamp":1690289000000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/199\/8\/1153\/40062\/T-bet-Controls-Autoaggressive-CD8-Lymphocyte"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4,19]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,4,19]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20031873","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2004,4,19]]}}}