Consequences of in situ production of IL-2 for islet cell death

Transgenic mice that expressed a single-copy IL-2 transgene in their pancreatic beta cells were previously shown to develop a massive inflammation in and around the islets, but did not progress to diabetes. When these mice were made homozygous for the transgene, diabetes did ensue in most animals by 200 days. Analysis of the T cells present in the pancreatic infiltrates of single-copy and homozygous rat insulin promoter IL-2 mice showed a predominance of CD4+ cells which was especially apparent in the very young mice. Furthermore, many of the CD4+ T cells in young mice displayed a memory-like phenotype in that they expressed higher levels of adhesion molecules and the IL-2R p55 marker. When the IL-2 transgene was introduced into nude mice, an almost identical pathology of inflammation was seen except that the infiltrating cells were mostly B cells. Expression of the same transgene in scid mice also resulted in an inflammatory response and in some situations it was sufficient to induce diabetes. From these results it appears that the T cell product, IL-2, in the absence of antigen-specific T or B cells can induce an inflammatory response of sufficient intensity to cause diabetes.