INTERLEUKIN-12 ADMINISTRATION INDUCES T-HELPER TYPE-1 CELLS AND ACCELERATES AUTOIMMUNE DIABETES IN NOD MICE

T cells play a major role in the development of insulin-dependent diab etes mellitus (IDDM) in nonobese diabetic (NOD) mice. Administration o f interleukin 12 (IL-12), a key cytokine which guides the development of T helper type 1 (Th1) CD4(+) T cells, induces rapid onset of IDDM i n NOD, but not in BALB/c mice. Histologically, IL-12 administration in duces massive infiltration of lymphoid cells, mostly T cells, in the p ancreatic islets of NOD mice. CD4(+) pancreas-infiltrating T cells, af ter activation by insolubilized anti T cell receptor antibody, secrete high levels of interferon gamma and low levels of IL-4. Therefore, IL -12 administration accelerates IDDM development in genetically suscept ible NOD mice, and this correlates with increased Th1 cytokine product ion by islet-infiltrating cells. These results hold implications for t he pathogenesis, and possibly for the therapy of IDDM and of other Th1 cell-mediated autoimmune diseases.