The phenotype of lymphoid cells and thymic epithelium correlates with development of autoimmune insulitis in NOD in equilibrium with C57BL/6 allophenic chimeras.

Abstract

The mechanisms contributing to the development of autoimmune insulin-dependent diabetes mellitus have been analyzed in allophenic mouse chimeras of the NOD in equilibrium with C57BL/6 strain combination (where NOD is nonobese diabetic). Occurrence of lymphoid cell infiltration (insulitis) in pancreatic islets was observed in the majority of such chimeras. The development of insulitis was found to correlate with major histocompatibility complex chimerism in lymphoid cells and in thymus cortical regions. Chimeras with more than 50% of C57BL/6 lymphoid cells rarely developed insulitis. Our data suggest that the correlation with the thymic cortical region is absolute. Thus, all individuals displaying NOD or NOD/C57BL/6 thymic cortical regions developed insulitis, whereas we have not observed insulitis in chimeras with only C57BL/6 thymic cortical regions. Thus the positive selection of T cells appears to play a crucial role in the development of insulin-dependent diabetes mellitus.