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 alpha and beta chains. In both TCRbeta and TCRalphabeta transgenic NOD mice the beta chain transgene was expressed by >98% of peripheral T cells. The alpha 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 beta chain and with depletion of the endogenous TCR V(beta) genes. Nonetheless, NOD animals transgenic for TCRbeta and TCRalphabeta developed diabetes similar to controls. Thus, skewing the TCR repertoire did not diminish autoimmune susceptibility in NOD mice.