Myosin-induced acute myocarditis is a T cell-mediated disease.
The heart is a target organ in several autoimmune diseases, and therefore it is important to understand more about the effector cells involved in immune-mediated mechanisms of myocardial cell death. Because immune T lymphocytes are central to many immune responses, we wanted to study the role of T cells in causing cardiac specific inflammation. We used purified mouse cardiac myosin to cause acute myocarditis in mice. The adoptive transfer of purified T cells from C.B-17 mice with active myocarditis to SCID recipients successfully transferred the disease into SCID hosts. In contrast, transfer of serum with high-titer antimyosin antibodies to SCID hosts did not cause myocarditis. Using mAb to deplete A/J mice of CD4+ T cells, we showed that these mice were protected against the induction of myocarditis. Depletion of CD8+ T cells reduced the severity of inflammation but did not prevent induction of myocarditis. We were also able to prevent the induction of myocarditis using major histocompatibility class II protein-binding, nonimmunogenic, competitor peptides. These blocking studies also indicated that in H-2k mice, myocarditis is an I-Ak-restricted disease, and provided further evidence that CD4+ T cells are critical to the induction of disease. Together, these studies provide direct evidence that myosin-induced myocarditis is a T cell-mediated disease.
Smith
S C
SC
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Allen
P M
PM
D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000517:prevention & control; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007114:Immunization; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000209:etiology* / Q000517:prevention & control; D009218:Myosins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D009218:Myosins