NON-DIABETOGENIC INSULITIS IN NOD[--]B1O.GD ALLOPHENIC MICE IN SPITE OF PERMISSIVE CLASS-I MHC ANTIGENS

Allophenic mice (embryo aggregation mouse chimeras) enable us to disse ct the process of spontaneous autoimmunity under physiological conditi ons. Our previous experiments showed that the autoimmune process in al lophenic mice of the NOD<->C57B1/6 strain combination does not progres s from insulitis to diabetes. One possible explanation for this protec tion is that H-2 K-d-restricted CD8(+) T cells kill only NOD beta cell s (K-d, D-b) in the chimeric islets, while the B6 beta cells (K-b, D-b ) are spared from destruction. To test this hypothesis we analysed 22 NOD<->B10.GD chimeras in which the class I MHC are shared by both pare ntal strains. Therefore all the beta cells in these chimeras express H -2 K-d molecules. Ten allophenic mice were killed at 7 weeks and studi ed for early pathology. No evidence for intra-islet infiltration was o btained at this age, suggesting that the autoimmune process in NOD<->B 10.GD chimeras is slower than in NOD mice. Twelve chimeras were follow ed up for 1 year for disease development and all failed to progress to full-blown diabetes, despite the occurrence of intra-insulitis in six out of 12 mice. The lack of disease in NOD<->B10.GD chimeras demonstr ates that class I MHC chimerism does not account for diabetes resistan ce in NOD-allophenic mice.