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

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
Free PMC article

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

N Itoh et al. J Exp Med. .
Free PMC article

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.

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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.
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References

    1. Castano L, Eisenbarth GS. Type I diabetes: a chronic autoimmune disease of human, mouse and rat. Annu Rev Immunol. 1990;8:647–679. - PubMed
    1. Bach JF. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev. 1994;15:516–542. - PubMed
    1. Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PGF, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985;313:353–360. - PubMed
    1. Itoh N, Hanafusa T, Miyazaki A, Miyagawa J, Yamagata K, Yamamoto K, Waguri M, Imagawa A, Tamura S, Inada M, et al. Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients. J Clin Invest. 1993;92:2313–2322. - PMC - PubMed
    1. Somoza N, Vargas F, Roura-Mir C, Vives-Pi M, Fernandez-Figueras MT, Ariza A, Gomis R, Bragado R, Marti M, Jaraquemada D, Pujol-Borrell R. Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor V beta usage, and cytokine profile. J Immunol. 1994;153:1360–1377. - PubMed

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