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

Eur J Immunol. 1992 May;22(5):1115-21. doi: 10.1002/eji.1830220503.

Abstract

Transgenic mice expressing murine interleukin (IL)-2 constitutively in islet beta 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-2Kb molecules known to induce tolerance by a peripheral mechanism when the RIP-IL-2 mice were mated to other mice expressing H-2Kb in islet beta cells (RIP-Kb 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmunity*
  • H-2 Antigens / immunology
  • Interferon-gamma / analysis
  • Interleukin-2 / analysis
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology*
  • Islets of Langerhans / chemistry*
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Pancreatitis / etiology*

Substances

  • H-2 Antigens
  • H-2Kb protein, mouse
  • Interleukin-2
  • Interferon-gamma