Cell
Volume 89, Issue 1, 4 April 1997, Pages 17-24
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Article
The Role of Fas in Autoimmune Diabetes

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Abstract

Immunologically privileged sites express Fas ligand (FasL), which protects them from attack by activated T cells that express Fas and die upon contact with FasL. In an attempt to protect nonobese diabetic mice (NOD) from autoimmune diabetes, we made FasL transgenic NOD mice using the β cell-specific rat insulin-1 promoter. Surprisingly, these transgenic mice showed heightened sensitivity to diabetogenic T cells, which was due to self-destruction of β cells upon T cell-mediated induction of Fas. Fas-negative NODlpr/lpr animals were resistant to diabetogenic T cells and to spontaneous diabetes. Thus, induction of Fas expression on β cells and their subsequent destruction constitutes the main pathogenic mechanism in autoimmune diabetes.

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