Role of Donor MHC Class III Genes in the Destruction of Transplanted Islets in NOD Mice

• Published in: Annals of the New York Academy of Sciences 2002-04, Vol.958 (1), p.175-178
• Main Authors: JEVNIKAR, ANTHONY M., PRANGE, SEAN, ZUCKER, PETER, SINGH, BHAGIRATH
• Format: Article
• Language: English
• Subjects: Animals; autoimmunity; Cell Survival; Gene Deletion; Graft Survival - genetics; Graft Survival - immunology; Histocompatibility Antigens - genetics; Histocompatibility Antigens - immunology; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class II - genetics; Islets of Langerhans - cytology; Islets of Langerhans Transplantation - immunology; Islets of Langerhans Transplantation - pathology; knockout; Major Histocompatibility Complex - genetics; MHC; Mice; Mice, Inbred NOD; NOD mice; Time Factors
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2002.tb02964.x

: MHC class III genes are important in immune regulation and inflammation, and the gene products of this region are well conserved between species. Their role in diabetes is, however, unknown. We used islets from NOD mice that lacked expression of both MHC class I and class II molecules to test the effect of class III differences on the injury of transplanted NOD islets. Loss of islet MHC class I was highly protective, while deletion of MHC class II had no benefit on islet survival. However the combined absence of both MHC class I and class II expression by NOD islets resulted in a delayed form of injury, when islets were transplanted to NOD mice. As neither MHC class I or II molecules were expressed by donor islet tissue, these results suggest a previously unrecognized and important contribution of MHC class III differences on islet injury following transplantation.