CONSEQUENCES OF IN-SITU PRODUCTION OF IL-2 FOR ISLET-CELL DEATH

Transgenic mice that expressed a single-copy IL-2 transgene in their p ancreatic beta cells were previously shown to develop a massive inflam mation in and around the islets, but did not progress to diabetes. Whe n these mice were made homozygous for the transgene, diabetes did ensu e in most animals by 200 days. Analysis of the T cells present in the pancreatic infiltrates of single-copy and homozygous rat insulin promo ter IL-2 mice showed a predominance of CD4(+) cells which was especial ly apparent in the very young mice. Furthermore, many of the CD4(+) T cells in young mice displayed a memory-like phenotype in that they exp ressed higher levels of adhesion molecules and the IL-2R p55 marker. W hen the IL-2 transgene was introduced into nude mice, an almost identi cal pathology of inflammation was seen except that the infiltrating ce lls were mostly B cells. Expression of the same transgene in scid mice also resulted in an inflammatory response and in some situations it w as sufficient to induce diabetes. From these results it appears that t he T cell product, IL-2, in the absence of antigen-specific T or B cel ls can induce an inflammatory response of sufficient intensity to caus e diabetes.