title: Induction of autoimmune myocarditis in interleukin-2-deficient mice.
abstract: BACKGROUND
  Interleukin (IL)-2 is an important growth and survival factor for T cells and plays a crucial role in inflammation. Myosin-induced myocarditis is strictly dependent on activated T cells and is a model for postinfectious inflammatory heart disease in humans. To explore the role of IL-2 in myocarditis, we injected mice genetically deficient for IL-2 with cardiac myosin. Because it is conceivable that the lack of IL-2 either promotes or ameliorates the disease, we selected mouse strains that differ in their susceptibility to cardiac myosin-induced myocarditis.
  
  
  RESULTS
  Mice from a susceptible strain (C3H) that were rendered IL-2 deficient by gene targeting (IL-2-/- mice) and littermate controls were immunized twice with purified cardiac myosin at a 7-day interval. Three weeks after the first immunization, hearts were obtained for histopathological and immunohistochemical analysis. Sera were tested for autoantibodies to the cardiac myosin isoform by enzyme-linked immunosorbent assay. The majority of C3H IL-2-/- mice developed severe myocarditis accompanied by high-titer myosin autoantibodies. In C57BL/6 mice, which develop only little myocarditis on myosin immunization, lack of IL-2 did not increase susceptibility to the disease. Moreover, the composition of the inflammatory infiltrate in C3H IL-2-/- mice was virtually identical to that seen in the wild-type strain.
  
  
  CONCLUSIONS
  Our data provide the first genetic evidence that in cardiac myosin-immunized mice, IL-2 has no essential role for the development of autoimmune heart disease and the generation of myosin autoantibodies.
authors.affiliation: Department of Pediatrics, University of Innsbruck, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Grässl
authors.forename: C L
authors.initials: CL
authors.lastname: Pummerer
authors.forename: I
authors.initials: I
authors.lastname: Horak
authors.forename: N
authors.initials: N
authors.lastname: Neu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology*; D004198:Disease Susceptibility; D007114:Immunization; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000209:etiology*; D009206:Myocardium / Q000276:immunology; D009218:Myosins / Q000008:administration & dosage / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007376:Interleukin-2; D009218:Myosins