SPECIFIC DESTRUCTION OF ISLET TRANSPLANTS IN NOD[--]C57BL 6 AND NOD[--]C3H/TIF EMBRYO AGGREGATION CHIMERAS IRRESPECTIVE OF ALLELIC DIFFERENCES IN BETA-CELL ANTIGENS/

We have tested the hypothesis that allelic differences in the antigens expressed by the beta-cells of the islets of Langerhans influence the development of insulitis in the non-obese diabetic (NOD) mouse. Islet s of Langerhans from NOD, C57BL/6 and C3H/Tif mice were transplanted u nder the kidney capsule of NOD<->C57BL/6 and NOD<->3H/Tif embryo aggre gation (EA) chimeras and the infiltration was scored 5-7 weeks later. Mononuclear cell infiltration of pancreatic islets was observed in 60% of NOD<->C57BL/6 and in 55% of the NOD<->C3H/Tif EA chimeras. All tra nsplanted EA chimeras that developed insulitis also displayed mono-nuc lear cell infiltrates in the transplants, irrespective of the origin o f the transplanted islets. In contrast, no infiltration of transplants was detected in EA chimeras scoring negative for insulitis. These res ults demonstrate that the specific destruction of islet transplants do es not require the expression of NOD specific antigens by the islets. Moreover, the beta-cell destruction appears not to be restricted to NO D-MHC. The correlation between insulitis and transplant beta-cell dest ruction suggests the possibility that the development of insulitis is a prerequisite for transplant specific destruction. MHC restricted des truction may, therefore, precede the beta-cell destruction of transpla nted islets. The chimerism among the mononuclear cells infiltrating th e islet transplants was found to correlate with the overall haematopoe tic chimerism in each of the individual EA chimeras. This observation suggests that NOD bone marrow, as well as non-NOD bone marrow, generat es cells contributing to the beta-cell destruction process.