TRANSGENIC MICE EXPRESSING CONSTITUTIVE LEVELS OF IL-2 IN ISLET BETA-CELLS DEVELOP DIABETES

IL-2 plays an important role in the clonal expansion of T cells during an immune response and it has been implicated in autoimmune disease. To examine the role of IL-2 in the regulation of peripheral tolerance we produced transgenic mice in which the expression of murine IL-2 was directed by the rat insulin II promoter. The IL-2 transgene was expre ssed specifically in the pancreas. Islets from transgenic mice synthes ized biologically active IL-2. Expression of IL-2 in the pancreas resu lted in a massive inflammatory response directed at the beta cells of the pancreas. The infiltrate consisted primarily of B cells and CD4(+) and CD8(+) T cells. The infiltrate resulted in destruction of the ins ulin-producing beta cells and diabetes, but there was no evidence for antigen specificity. The results suggest that local IL-2 production el icits the recruitment and activation of cells capable of destroying be ta cells by non-antigen-specific mechanisms.