NOD congenic mice genetically protected from autoimmune diabetes remain resistant to transplantation tolerance induction.
Document Type
Article
Publication Date
2003
Keywords
Antibodies-Monoclonal, Antibody-Specificity, Blood-Transfusion, CD40-Ligand, Diabetes-Mellitus-Insulin-Dependent, Genetic-Predisposition-to-Disease, Graft-Survival, Immunity-Natural, Mice, Mice-Inbred-C57BL, Mice-Inbred-NOD, Skin-Transplantation, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Time-Factors, Transplantation-Tolerance
First Page
321
Last Page
326
JAX Source
Diabetes 2003 Feb; 52(2):321-6.
Abstract
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.
Recommended Citation
Pearson T,
Markees TG,
Wicker LS,
Serreze DV,
Peterson LB,
Mordes JP,
Rossini AA,
Greiner DL.
NOD congenic mice genetically protected from autoimmune diabetes remain resistant to transplantation tolerance induction. Diabetes 2003 Feb; 52(2):321-6.