Fas Stimulation Results in Selective Islet Infiltrate Apoptosis in Situ and Reversal of Diabetes

Breakdown of peripheral T cell regulation due to defective antigen-activated apoptosis may lead to autoimmunity. In the nonobese diabetic (NOD) mouse model of type 1 diabetes mellitus, we have demonstrated defects in T cell activation and peripheral apoptosis. Stimulation of the Fas pathway by a Fas receptor agonist led to enhanced in vitro apoptosis and in vivo selective apoptosis of islet-infiltrating lymphocytes. Administration of the Fas agonist immediately after onset of diabetes led to reversal of diabetes in NOD mice. Inducing peripheral T cell apoptosis may be a potential method for reversal of autoimmune diabetes.