{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:30:08Z","timestamp":1792222208613,"version":"4.4.0"},"reference-count":44,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,9,1]]},"abstract":"<jats:p>T cell\u2013specific adaptor protein (TSAd) is a T lineage\u2013restricted signaling adaptor molecule that is thought to participate in the assembly of intracellular signaling complexes in T cells. Previous studies of TSAd-deficient mice have revealed a role for TSAd in the induction of T cell interleukin 2 secretion and proliferation. We now show that TSAd-deficient mice are susceptible to lupus-like autoimmune disease. On the nonautoimmune-prone C57BL\/6 genetic background, TSAd deficiency results in hypergammaglobulinemia that affects all immunoglobulin (Ig)G subclasses. Older C57BL\/6 TSAd-deficient mice (1 yr of age) accumulate large numbers of activated T and B cells in spleen, produce autoantibodies against a variety of self-targets including single stranded (ss) and double stranded (ds) DNA, and, in addition, develop glomerulonephritis. We further show that immunization of younger C57BL\/6 TSAd-deficient mice (at age 2 mo) with pristane, a recognized nonspecific inflammatory trigger of lupus, results in more severe glomerulonephritis compared with C57BL\/6 controls and the production of high titer ss and ds DNA antibodies of the IgG subclass that are not normally produced by C57BL\/6 mice in this model. The development of autoimmunity in TSAd-deficient mice is associated with defective T cell death in vivo. These findings illustrate the role of TSAd as a critical regulator of T cell death whose absence promotes systemic autoimmunity.<\/jats:p>","DOI":"10.1084\/jem.20021358","type":"journal-article","created":{"date-parts":[[2003,9,2]],"date-time":"2003-09-02T19:07:00Z","timestamp":1062529620000},"page":"809-821","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":53,"title":["Impaired T Cell Death and Lupus-like Autoimmunity in T Cell\u2013specific Adapter Protein\u2013deficient Mice"],"prefix":"10.1084","volume":"198","author":[{"given":"Jorn","family":"Drappa","sequence":"first","affiliation":[{"name":"1Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn A.","family":"Kamen","sequence":"additional","affiliation":[{"name":"1Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021"},{"name":"2Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Chan","sequence":"additional","affiliation":[{"name":"1Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Georgiev","sequence":"additional","affiliation":[{"name":"1Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalit","family":"Ashany","sequence":"additional","affiliation":[{"name":"1Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Marti","sequence":"additional","affiliation":[{"name":"1Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021"},{"name":"2Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D.","family":"King","sequence":"additional","affiliation":[{"name":"1Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021"},{"name":"2Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2003,9,2]]},"reference":[{"key":"2023072512160996300_BIB1","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1074\/jbc.273.8.4539","volume":"273","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2023072512160996300_BIB2","doi-asserted-by":"crossref","first-page":"5242","DOI":"10.4049\/jimmunol.163.10.5242","volume":"163","year":"1999","journal-title":"J. Immunol."},{"key":"2023072512160996300_BIB3","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1084\/jem.190.11.1657","volume":"190","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072512160996300_BIB4","doi-asserted-by":"crossref","first-page":"5093","DOI":"10.1074\/jbc.M003719200","volume":"276","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2023072512160996300_BIB5","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1084\/jem.193.12.1425","volume":"193","year":"2001","journal-title":"J. Exp. Med."},{"key":"2023072512160996300_BIB6","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.4049\/jimmunol.159.4.2058","volume":"159","year":"1997","journal-title":"J. Immunol."},{"key":"2023072512160996300_BIB7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0065-2776(08)60342-9","volume":"37","year":"1985","journal-title":"Adv. Immunol."},{"key":"2023072512160996300_BIB8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.iy.09.040191.001331","volume":"9","year":"1991","journal-title":"Annu. Rev. Immunol."},{"key":"2023072512160996300_BIB9","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0090-1229(88)90066-9","volume":"47","year":"1988","journal-title":"Clin. Immunol. Immunopathol."},{"key":"2023072512160996300_BIB10","first-page":"204","volume":"2","year":"1975","journal-title":"J. Rheumatol."},{"key":"2023072512160996300_BIB11","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/art.1780170605","volume":"17","year":"1974","journal-title":"Arthritis Rheum."},{"key":"2023072512160996300_BIB12","first-page":"1211","volume":"2","year":"1983","journal-title":"Lancet."},{"key":"2023072512160996300_BIB13","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1084\/jem.180.6.2341","volume":"180","year":"1994","journal-title":"J. Exp. Med."},{"key":"2023072512160996300_BIB14","doi-asserted-by":"crossref","first-page":"10934","DOI":"10.1073\/pnas.92.24.10934","volume":"92","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072512160996300_BIB15","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1084\/jem.188.5.985","volume":"188","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072512160996300_BIB16","first-page":"399","volume":"121","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"2023072512160996300_BIB17","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.4049\/jimmunol.165.2.1036","volume":"165","year":"2000","journal-title":"J. Immunol."},{"key":"2023072512160996300_BIB18","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/349245a0","volume":"349","year":"1991","journal-title":"Nature."},{"key":"2023072512160996300_BIB19","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/373441a0","volume":"373","year":"1995","journal-title":"Nature."},{"key":"2023072512160996300_BIB20","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/373438a0","volume":"373","year":"1995","journal-title":"Nature."},{"key":"2023072512160996300_BIB21","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/373444a0","volume":"373","year":"1995","journal-title":"Nature."},{"key":"2023072512160996300_BIB22","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/S1074-7613(02)00322-9","volume":"16","year":"2002","journal-title":"Immunity."},{"key":"2023072512160996300_BIB23","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0952-7915(02)00335-7","volume":"14","year":"2002","journal-title":"Curr. Opin. Immunol."},{"key":"2023072512160996300_BIB24","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1016\/S0092-8674(02)00704-3","volume":"109","year":"2002","journal-title":"Cell."},{"key":"2023072512160996300_BIB25","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1073\/pnas.072088099","volume":"99","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072512160996300_BIB26","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1128\/MCB.22.11.3610-3620.2002","volume":"22","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2023072512160996300_BIB27","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1101\/gad.13.11.1367","volume":"13","year":"1999","journal-title":"Genes Dev."},{"key":"2023072512160996300_BIB28","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1093\/emboj\/18.8.2049","volume":"18","year":"1999","journal-title":"EMBO J."},{"key":"2023072512160996300_BIB29","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1084\/jem.20020666","volume":"196","year":"2002","journal-title":"J. Exp. Med."},{"key":"2023072512160996300_BIB30","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0092-8674(93)80067-O","volume":"75","year":"1993","journal-title":"Cell."},{"key":"2023072512160996300_BIB31","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1002\/eji.1830251111","volume":"25","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"2023072512160996300_BIB32","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1126\/science.7770771","volume":"268","year":"1995","journal-title":"Science."},{"key":"2023072512160996300_BIB33","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/1074-7613(95)90180-9","volume":"3","year":"1995","journal-title":"Immunity."},{"key":"2023072512160996300_BIB34","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/83253","volume":"7","year":"2001","journal-title":"Nat. Med."},{"key":"2023072512160996300_BIB35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/35003228","volume":"403","year":"2000","journal-title":"Nature."},{"key":"2023072512160996300_BIB36","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1038\/ni721","volume":"2","year":"2001","journal-title":"Nat. Immunol."},{"key":"2023072512160996300_BIB37","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1126\/science.286.5445.1735","volume":"286","year":"1999","journal-title":"Science."},{"key":"2023072512160996300_BIB38","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0092-8674(00)00209-9","volume":"103","year":"2000","journal-title":"Cell."},{"key":"2023072512160996300_BIB39","doi-asserted-by":"crossref","first-page":"8661","DOI":"10.1073\/pnas.88.19.8661","volume":"88","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072512160996300_BIB40","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/0090-1229(85)90153-9","volume":"37","year":"1985","journal-title":"Clin. Immunol. Immunopathol."},{"key":"2023072512160996300_BIB41","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4049\/jimmunol.133.1.227","volume":"133","year":"1984","journal-title":"J. Immunol."},{"key":"2023072512160996300_BIB42","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1074-7613(00)80478-1","volume":"8","year":"1998","journal-title":"Immunity."},{"key":"2023072512160996300_BIB43","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nri822","volume":"2","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2023072512160996300_BIB44","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/sj.gene.6363774","volume":"2","year":"2001","journal-title":"Genes Immun."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/198\/5\/809\/1711991\/jem1985809.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/198\/5\/809\/1711991\/jem1985809.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T12:26:26Z","timestamp":1690287986000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/198\/5\/809\/39877\/Impaired-T-Cell-Death-and-Lupus-like-Autoimmunity"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,1]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2003,9,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20021358","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2003,9,1]]}}}