Diabetes induction in C57BL/6 mice reconstituted with lymphocytes of nonobese diabetic <-> C57BL/6 mouse embryo aggregation chimeras

To determine whether the genetic background of the insulin-producing beta c ells of the pancreas contributes to autoimmune diabetes susceptibility, we have used a model of the disease based on tranferring spleen cells from non obese diabetic (NOD) <-> C57BL/6 (B6) embryo aggregation (EA) chimeras into B6 and NOD irradiated mice. Insulitis and diabetes could be induced into b oth B6 and NOD hosts, albeit with low incidence. Cyclophosphamide (CY) trea tment, known to accelerate diabetes in prediabetic NOD mice, was found to i ncrease diabetes incidence up to 50-60% in both B6 and NOD mice reconstitut ed with chimeric splenocytes, while diabetes did not occur in CY-treated B6 mice reconstituted with B6 splenocytes. We conclude that the genetic make- up of the target organ does not affect the final stage of the pathogenesis of insulin-dependent diabetes mellitus.