Format

Send to

Choose Destination
Cell Death Differ. 2010 Apr;17(4):577-85. doi: 10.1038/cdd.2009.165. Epub 2009 Nov 20.

The role of perforin and granzymes in diabetes.

Author information

1
Department of Immunology and Diabetes, St Vincent's Institute, 41 Victoria Parade, Fitzroy, Melbourne 3065, Australia. hthomas@svi.edu.au

Abstract

Type 1 diabetes results from autoimmune destruction of pancreatic beta-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 beta-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 beta-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 pathway in beta-cell destruction in type I diabetes and allogeneic islet graft rejection make this pathway an important target for blockade in future therapies for type I diabetes. In addition, granzymes have a newly recognized role in inflammation, a feature of both type I and II diabetes, suggesting their role should be further explored in both the common forms of diabetes.

PMID:
19927156
DOI:
10.1038/cdd.2009.165
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center