Diabetes Induction in C57BL/6 Mice Reconstituted with Lymphocytes of Nonobese Diabetic <−> C57BL/6 Mouse Embryo Aggregation Chimeras

Abstract

To determine whether the genetic background of the insulin-producing beta cells of the pancreas contributes to autoimmune diabetes susceptibility, we have used a model of the disease based on transferring spleen cells from nonobese diabetic (NOD) <--> C57BL/6 (B6) embryo aggregation (EA) chimeras into B6 and NOD irradiated mice. Insulitis and diabetes could be induced into both B6 and NOD hosts, albeit with low incidence. Cyclophosphamide (CY) treatment, known to accelerate diabetes in prediabetic NOD mice, was found to increase diabetes incidence up to 50-60% in both B6 and NOD mice reconstituted 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.

CTLA-4 +49A/G gene polymorphism and type 1 diabetes mellitus in the Chinese population: a meta-analysis of 2238 subjects

“…CTLA-4 could negatively regulate T cell proliferation. In 1998, Colucci et al found deficiency in CTLA-4 expression in non-obese diabetic (NOD) mice, suggesting that CTLA-4 might be involved in the pathogenesis of T1DM [28]. In 2004, Vijayakrishnan et al found that the expression of ligand-independent CTLA-4 (liCTLA-4) lacking B7-binding domain signals was higher in memory/regulatory T cells from diabetes-resistant NOD congenic mice compared with susceptible NOD mice.…”