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(Circulation. 1997;95:1773-1776.)
© 1997 American Heart Association, Inc.

Articles

Induction of Autoimmune Myocarditis in Interleukin-2–Deficient Mice

Gerhard Grässl, MD; Christian L. Pummerer, MD; Ivan Horak, MD; Nikolaus Neu, MD

From the Department of Pediatrics (G.G., C.L.P., N.N.), University of Innsbruck, Austria, and the Institute of Virology and Immunobiology (I.H.), University of Würzburg, Federal Republic of Germany.

Correspondence to Dr Nikolaus Neu, Univ-Klinik für Kinderheilkunde, Anichstraße 35, A-6020 Innsbruck, Austria.

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.

Methods and 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.

Key Words: myocarditis • immunology • myosin • interleukins