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. 1997 Aug 18;186(4):613-8.
doi: 10.1084/jem.186.4.613.

"VSports在线直播" Requirement of Fas for the development of autoimmune diabetes in nonobese diabetic mice

N Itoh  1 , A Imagawa, T Hanafusa, M Waguri, K Yamamoto, H Iwahashi, M Moriwaki, H Nakajima, J Miyagawa, M Namba, S Makino, S Nagata, N Kono, Y Matsuzawa
Affiliations

Requirement of Fas for the development of autoimmune diabetes in nonobese diabetic mice

N Itoh et al. J Exp Med. .

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 VSports手机版. 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. .

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Figures

Figure 1
Figure 1
Fas mRNA expression in the thymus (A), Fas expression on thymocytes (B), and two-color flow cytometric analysis of cell surface markers on splenocytes (C) of NOD-+/+ and NOD-lpr/lpr.
Figure 2
Figure 2
Cumulative incidence of spontaneous diabetes in female NOD-+/+ (n = 19), NOD-+/lpr (n = 18), and NOD-lpr/lpr (n = 17).
Figure 3
Figure 3
Cumulative incidence of adoptively transferred diabetes in male NOD-+/+ (n = 9), NOD-+/lpr (n = 12), and NOD-lpr/lpr (n = 7).
Figure 4
Figure 4
Hematoxylin and eosin staining of pancreatic islets of NOD-+/+ (A) and NOD-lpr/lpr (B) transferred with splenocytes from diabetic NOD. Original magnification was 200.
Figure 4
Figure 4
Hematoxylin and eosin staining of pancreatic islets of NOD-+/+ (A) and NOD-lpr/lpr (B) transferred with splenocytes from diabetic NOD. Original magnification was 200.
See this image and copyright information in PMC

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