NOD congenic mice genetically protected from autoimmune diabetes remain resistant to transplantation tolerance induction
Authors
Pearson, ToddMarkees, Thomas G.
Wicker, Linda S.
Serreze, David V.
Peterson, Laurence B.
Mordes, John P.
Rossini, Aldo A.
Greiner, Dale L.
UMass Chan Affiliations
Department of Medicine, Division of Endocrinology and MetabolismDepartment of Medicine, Diabetes Division
Program in Immunology and Virology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2003-01-24Keywords
Animals; Antibodies, Monoclonal; Antibody Specificity; Blood Transfusion; CD40 Ligand; Diabetes Mellitus, Type 1; Genetic Predisposition to Disease; Graft Survival; Immunity, Natural; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Skin Transplantation; Time Factors; Transplantation ToleranceLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The loss of self-tolerance leading to autoimmune type 1 diabetes in the NOD mouse model involves at least 19 genetic loci. In addition to their genetic defects in self-tolerance, NOD mice resist peripheral transplantation tolerance induced by costimulation blockade using donor-specific transfusion and anti-CD154 antibody. Hypothesizing that these two abnormalities might be related, we investigated whether they could be uncoupled through a genetic approach. Diabetes-resistant NOD and C57BL/6 stocks congenic for various reciprocally introduced Idd loci were assessed for their ability to be tolerized. Surprisingly, in NOD congenic mice that are almost completely protected from diabetes, costimulation blockade failed to prolong skin allograft survival. In reciprocal C57BL/6 congenic mice with NOD-derived Idd loci, skin allograft survival was readily prolonged by costimulation blockade. These data indicate that single or multiple combinations of evaluated Idd loci that dramatically reduce diabetes frequency do not correct resistance to peripheral transplantation tolerance induced by costimulation blockade. We suggest that mechanisms controlling autoimmunity and transplantation tolerance in NOD mice are not completely overlapping and are potentially distinct, or that the genetic threshold for normalizing the transplantation tolerance defect is higher than that for preventing autoimmune diabetes.Source
Diabetes. 2003 Feb;52(2):321-6.
DOI
0.2337/diabetes.52.2.321Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34326PubMed ID
12540603Related Resources
ae974a485f413a2113503eed53cd6c53
0.2337/diabetes.52.2.321