Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin‐2 in islet β cells

Abstract

Transgenic mice expressing murine interleukin (IL)‐2 constitutively in islet β cells were generated (RIP‐IL‐2 mice). They died at an early age, when higher levels of IL‐2 were produced, because of a predominant macrophage inflammatory response that destroyed the exocrine pancreas. Animals with lower levels of IL‐2 survived and had islets that became increasingly infiltrated with lymphocytes over time. However, in spite of the presence of impressive peri‐ and intra‐islet infiltrates, autoimmunity to islet antigens was not seen. Autoimmunity was also not induced to extrathymic H‐2K^b molecules known to induce tolerance by a peripheral mechanism when the RIP‐IL‐2 mice were mated to other mice expressing H‐2K^b in islet β cells (RIP‐K^b mice). Apparently, IL‐2 can act only on activated T cells and is unable to reverse tolerance in T cells that have been made unresponsive through inappropriate presentation of antigen.