Apoptosis of pancreatic beta-cells detected in accelerated diabetes of NOD mice: no role of Fas-Fas ligand interaction in autoimmune diabetes.

Autoreactive T lymphocytes probably cause pancreatic beta-cell death by inducing apoptosis. To visualize apoptotic beta-cells in vivo, we accelerated diabetes of NOD mice with cyclophosphamide (CY) or adoptive transfer. We also studied whether Fas-mediated apoptosis is involved in the development of diabetes by administrating anti-Fas ligand (FasL) Ab and by grafting Fas-deficient neonatal pancreas from NOD-lpr/lpr mice. Apoptotic cells were clearly shown 8 days after CY treatment. Beta-cell apoptosis was also observed after adoptive transfer but in a different kinetic pattern. Anti-FasL Ab administration failed to inhibit diabetes after CY treatment or adoptive transfer, while it inhibited Con A-induced hepatitis. Fas-deficient neonatal pancreata were destroyed by lymphocytic infiltration in diabetic NOD mice. Our results clearly demonstrate apoptosis of beta-cells in accelerated diabetes and indicate that Fas-FasL interaction is not involved in diabetes of NOD mice, contrary to the previous reports.