The role of perforin and granzymes in diabetes

Abstract

Type 1 diabetes results from autoimmune destruction of pancreatic Β-cells by CD8+ T cells. The requirement for CD8+ T cells implicates perforin and granzymes as effectors of tissue destruction. Diabetogenic cytotoxic T cells kill Β-cells by the perforin/granzyme pathway in vitro. In the non-obese diabetic mouse model of type I diabetes, perforin deficiency results in a highly significant reduction in disease, indicating a direct role for perforin in Β-cell death in vivo, although other cell death pathways must account for the residual diabetes in perforin-deficient mice. Perforin and granzyme B are also important in allogeneic destruction of islets. The dominant role of the perforin/granzyme..