FOLLOWING A DIABETOGENIC T-CELL FROM GENESIS THROUGH PATHOGENESIS

Nonobese diabetic (NOD) mice spontaneously develop a disease very simi lar to type 1 diabetes in humans. We have generated a transgenic mouse strain carrying the rearranged T cell receptor genes from a diabetoge nic T cell clone derived from a NOD mouse. Self-reactive T cells expre ssing the transgene-encoded specificity are not tolerized in these ani mals, resulting in rampant insulitis and eventually diabetes. Features of the disease process emphasize two so-called check-points, recogniz ed previously in the NOD and human diseases but easily misinterpreted. Although NOD mice are protected from insulitis and diabetes by expres sion of the E molecule encoded in the major histocompatibility complex , the transgenics are not, permitting us to exclude some possible mech anisms of protection.