{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:45:07Z","timestamp":1790171107880,"version":"4.1.0"},"reference-count":31,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,8,18]]},"abstract":"<jats:p>Insulin-dependent diabetes mellitus (IDDM) is assumed to be a T cell\u2013mediated autoimmune disease. To investigate the role of Fas-mediated cytotoxicity in pancreatic \u03b2 cell destruction, we established nonobese diabetic (NOD)-lymphoproliferation (lpr)\/lpr mice lacking Fas. Out of three genotypes, female NOD-+\/+ and NOD-+\/lpr developed spontaneous diabetes by the age of 10 mo with the incidence of 68 and 62%, respectively. In contrast, NOD-lpr\/lpr did not develop diabetes or insulitis. To further explore the role of Fas, adoptive transfer experiments were performed. When splenocytes were transferred from diabetic NOD, male NOD-+\/+ and NOD-+\/lpr developed diabetes with the incidence of 89 and 83%, respectively, whereas NOD-lpr\/lpr did not show glycosuria by 12 wk after transfer. Severe mononuclear cell infiltration was revealed in islets of NOD-+\/+ and NOD-+\/lpr, whereas islet morphology remained intact in NOD-lpr\/lpr. These results suggest that Fas-mediated cytotoxicity is required to initiate \u03b2 cell autoimmunity in NOD mice. Fas\u2013Fas ligand system might be critical for autoimmune \u03b2 cell destruction leading to IDDM.<\/jats:p>","DOI":"10.1084\/jem.186.4.613","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"613-618","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":175,"title":["Requirement of Fas for the Development of Autoimmune Diabetes in Nonobese Diabetic Mice"],"prefix":"10.1084","volume":"186","author":[{"given":"Naoto","family":"Itoh","sequence":"first","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihisa","family":"Imagawa","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Hanafusa","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Waguri","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Iwahashi","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Moriwaki","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromu","family":"Nakajima","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichiro","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyoshi","family":"Namba","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Makino","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigekazu","family":"Nagata","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Kono","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; and \u2016Center for Experimental Animals Development, Shionogi & Co., Ltd., Koka, Shiga 520-34, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"From the *Department of Clinical Laboratory Science, School of Allied Health Sciences, \u2021Second Department of Internal Medicine, and \u00a7Department of Genetics, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan; 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