CD4(-ISLET CELL-REACTIVE T-CELL CLONES THAT SUPPRESS AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE() BETA)

We report the isolation of a panel of CD4(+) T helper type 1 autoreact ive T cell clones from the spleen of unprimed nonobese diabetic mice, a murine model of human insulin-dependent diabetes mellitus. The T cel l clones express a diverse repertoire of T cell receptors, three of wh ich recognize beta islet cell autoantigen(s). The islet cell-reactive T cell clones inhibit adoptive transfer of insulin-dependent diabetes mellitus and intraislet lymphocytic infiltration. The protective capac ity of the T cell clones correlates with their ability to produce a no vel immunoregulatory activity that potently inhibits in vitro allogene ic mixed lymphocyte reaction. The partially purified activity signific antly inhibited the adoptive transfer of diabetes. Our work provides e vidence in support of the existence of T helper type 1, CD4(+) T cells reactive to beta islet cell autoantigens that have acquired a protect ive instead of a diabetogenic effector function. These T cells mediate their protective action in part by production of an immunoregulatory activity capable of downregulating immune responses, and they are like ly to represent a population of regulatory T cells that normally plays a role in maintaining peripheral tolerance.