NOD Congenic Mice Genetically Protected From Autoimmune Diabetes Remain Resistant to Transplantation Tolerance Induction

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 transplanta-tion 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 uncou-pled through a genetic approach. Diabetes-resistant NOD and C57BL/6 stocks congenic for various recipro-cally introduced Idd loci were assessed for their ability to be tolerized. Surprisingly, in NOD congenic mice that are almost completely protected from diabetes, co-stimulation blockade failed to prolong skin allograft survival. In reciprocal C57BL/6 congenic mice wit