Published in Volume
102, Issue 6
(September 15, 1998)J Clin Invest.
1998, The American Society for
IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes.
Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia.
Published September 15, 1998
We have generated transgenic nonobese diabetic (NOD) mice expressing dominant negative mutant IFN-gamma receptors on pancreatic beta cells to investigate whether the direct effects of IFN-gamma on beta cells contribute to autoimmune diabetes. We have also quantitated by flow cytometry the rise in class I MHC on beta cells of NOD mice with increasing age and degree of islet inflammatory infiltrate. Class I MHC expression increases gradually with age in wild-type NOD mice; however, no such increase is observed in the transgenic beta cells. The transgenic mice develop diabetes at a similar rate to that of wild-type animals. This study dissociates class I MHC upregulation from progression to diabetes, shows that the rise in class I MHC is due to local IFN-gamma action, and eliminates beta cells as the targets of IFN-gamma in autoimmune diabetes.