1. Recombinant cardiac myosin fragment induces experimental autoimmune myocarditis via activation of Th1 and Th17 immunity
- Author
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Melvin D. Daniels, David M. Engman, Kegiang Wang, and Kenneth V. Hyland
- Subjects
Male ,Myocarditis ,Immunology ,Biology ,medicine.disease_cause ,Article ,Autoimmune Diseases ,Autoimmunity ,law.invention ,Interferon-gamma ,Mice ,Cardiac Myosins ,Immune system ,Immunity ,law ,medicine ,Animals ,Immunology and Allergy ,Cells, Cultured ,Interleukin 4 ,Interleukin-6 ,Interleukin-17 ,T-Lymphocytes, Helper-Inducer ,Th1 Cells ,medicine.disease ,Recombinant Proteins ,Mononuclear cell infiltration ,Recombinant DNA ,Interleukin-4 - Abstract
The specificity and function of T helper (Th) immune responses underlying the induction, progression, and resolution of experimental autoimmune myocarditis (EAM) in A/J mice are unclear. Published data suggest involvement of both Th1 and Th2 responses in EAM; however, the previous inability to assess antigen-specific in vivo and in vitro T-cell responses in cardiac myosin-immunized animals has confounded our understanding of this important model of autoimmune myocarditis. The goal of our study was to develop an alternative model of EAM based on a recombinant fragment of cardiac myosin, in hopes that the recombinant protein will permit measurement of functional T-cell responses that is not possible with purified native protein. A/J mice immunized with a recombinant fragment of cardiac myosin spanning amino acids 1074-1646, termed Myo4, developed severe myocarditis characterized by cardiac hypertrophy, massive mononuclear cell infiltration and fibrosis, three weeks post-immunization. The mice also developed an IgG1 dominant humoral immune response specific for both Myo4 and purified cardiac myosin. The in vitro stimulation of splenocytes harvested from Myo4-immunized animals with Myo4 resulted in cellular proliferation with preferential production of the Th1- and Th17-associated cytokines, IFN-gamma, IL-17, and IL-6, respectively. Production of IL-4 was negligible by comparison. This study describes a new model of EAM, inducible by immunization with a specific fragment of cardiac myosin, from which antigen-specific analyses reveal an importance for both Th1 and Th17 immunity.
- Published
- 2008