Elliott E A, Flavell R A
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.
Int Immunol. 1994 Nov;6(11):1629-37. doi: 10.1093/intimm/6.11.1629.
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 expressed specifically in the pancreas. Islets from transgenic mice synthesized biologically active IL-2. Expression of IL-2 in the pancreas resulted 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 insulin-producing beta cells and diabetes, but there was no evidence for antigen specificity. The results suggest that local IL-2 production elicits the recruitment and activation of cells capable of destroying beta cells by non-antigen-specific mechanisms.
