| First Author | Itoh N | Year | 1997 |
| Journal | J Exp Med | Volume | 186 |
| Issue | 4 | Pages | 613-8 |
| PubMed ID | 9254659 | Mgi Jnum | J:43117 |
| Mgi Id | MGI:1097132 | Doi | 10.1084/jem.186.4.613 |
| Citation | Itoh N, et al. (1997) Requirement of Fas for the development of autoimmune diabetes in nonobese diabetic mice. J Exp Med 186(4):613-8 |
| abstractText | 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. |
