title: Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin-2 in islet beta cells.
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.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Allison
authors.forename: L
authors.initials: L
authors.lastname: Malcolm
authors.forename: N
authors.initials: N
authors.lastname: Chosich
authors.forename: J F
authors.initials: JF
authors.lastname: Miller
mesh_terms: D000818:Animals; D015551:Autoimmunity; D006183:H-2 Antigens / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007515:Islets of Langerhans / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010195:Pancreatitis / Q000209:etiology*
chemical_list: D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007376:Interleukin-2; D007371:Interferon-gamma