title: Requirement of Fas for the development of autoimmune diabetes in nonobese diabetic mice.
abstract: Insulin-dependent diabetes mellitus (IDDM) is assumed to be a T cell-mediated autoimmune disease. To investigate the role of Fas-mediated cytotoxicity in pancreatic beta 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 beta cell autoimmunity in NOD mice. Fas-Fas ligand system might be critical for autoimmune beta cell destruction leading to IDDM.
authors.affiliation: Department of Clinical Laboratory Science, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Suita, Osaka 565, Japan. nitoh@sahs.med.osaka-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Itoh
authors.forename: A
authors.initials: A
authors.lastname: Imagawa
authors.forename: T
authors.initials: T
authors.lastname: Hanafusa
authors.forename: M
authors.initials: M
authors.lastname: Waguri
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Iwahashi
authors.forename: M
authors.initials: M
authors.lastname: Moriwaki
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: J
authors.initials: J
authors.lastname: Miyagawa
authors.forename: M
authors.initials: M
authors.lastname: Namba
authors.forename: S
authors.initials: S
authors.lastname: Makino
authors.forename: S
authors.initials: S
authors.lastname: Nagata
authors.forename: N
authors.initials: N
authors.lastname: Kono
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018895:Microsatellite Repeats; D010641:Phenotype; D013601:T-Lymphocytes / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D019014:fas Receptor