Type I diabetes and multiple sclerosis patients target islet plus central nervous system autoantigens; Nonimmunized nonobese diabetic mice can develop autoimmune encephalitis

Type I diabetes and multiple sclerosis (MS) are distinct autoimmune disease s where T cells target either islet or CNS self-proteins. Unexpectedly, we found that autoreactive T cells in diabetic patients, relatives with high d iabetes risk, nonobese diabetic (NOD) mice, and MS patients routinely targe t classical islet as well as CNS autoantigens. The pathogenic potential of CNS autoreactivity was testable in NOD mice. Pertussis holotoxin, without a dditional Ags or adjuvants, allowed development of an NOD mouse-specific, a utoimmune encephalitis with variable primary-progressive, monophasic, and r elapsing-remitting courses, T cells from diabetic donors transferred CNS di sease to pertussis toxin-pretreated NOD,scid mice, with accumulation of CD3 /IFN-gamma transcripts in the brain. Diabetes and MS appear more closely re lated than previously perceived. NOD mouse-specific, autoimmune encephaliti s provides a new MS model to identify factors that determine alternative di sease outcomes in hosts with similar autoreactive T cell repertoires.