IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes

Author(s): Thomas, HE; Parker, JL; Schreiber, RD; Kay, TWH;
Details: Publication Year 1998-09-15,Volume 102,Issue #6,Page 1249-1257
Journal Title: JOURNAL OF CLINICAL INVESTIGATION
Publication Type: Journal Article
Abstract: 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.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: HISTOCOMPATIBILITY COMPLEX ANTIGENS; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; NOD MICE; GENE-EXPRESSION; MONOCLONAL-ANTIBODIES; TRANSGENE EXPRESSION; ADHESION MOLECULES; VIRUS-INFECTION
Publisher's Version: https://doi.org/10.1172/JCI2899
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1998-09-15 12:00:00