Beta cell apoptosis in T cell-mediated autoimmune diabetes.

Abstract

Insulin-dependent diabetes mellitus results from T cell-mediated destruction of insulin-producing, pancreatic islet beta cells. How this destruction takes place has remained elusive--largely due to the slow kinetics of disease progression. By crossing a transgenic mouse carrying a beta cell-specific T cell receptor onto the NOD.scid background, we produced a simplified but robust and accelerated model of diabetes. This mouse produces CD4+ T cells bearing transgenic T cell receptor but is devoid of CD8+ T cells and B cells. More importantly, this mouse develops a rapid diabetes, which has allowed us to record and quantify beta cell death. We have determined that beta cells within the inflamed islets die by apoptosis.