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

Abstract

Autoreactive T lymphocytes probably cause pancreatic β‐cell death by inducing apoptosis. To visualize apoptotic β‐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. β‐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 β‐cells in accelerated diabetes and indicate that Fas‐FasL interaction is not involved in diabetes of NOD mice, contrary to the previous reports.