Progression to Diabetes in Nonobese Diabetic (NOD) mice with transgenic T cell receptors

The T cell receptor (TCR) requirements in the pathogenesis of insulin-dependent diabetes were examined with transgenic NOD mice bearing nondisease-related TCR α and β chains. In both TCRβ and TCRαβ transgenic NOD mice the β chain transgene was expressed by >98% of peripheral T cells. The αa chain transgene was also highly expressed. Insulitis developed in both sets of transgenic animals with most of the lymphocytes in the lesion expressing the transgenic β chain and with depletion of the endogenous TCRV genes. Nonetheless, NOD animals transgenic for TCRβ and TCRαβ developed diabetes similar to controls. Thus, skewing the TCR repertoire did not diminish autoimmune susceptibility in NOD mice.