In Vivo Significance of T Cells in the Development of Coxsackievirus B3 Myocarditis in Mice Immature but Antigen-Specific T Cells Aggravate Cardiac Injury

• Published in: Circulation research Vol. 67; no. 3; pp. 589 - 598
• Main Authors: Kishimoto, Chiharu, Abelmann, Walter H
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.09.1990
• Subjects: Animals; Antibodies, Viral - analysis; Coxsackievirus Infections - immunology; Coxsackievirus Infections - pathology; Enterovirus B, Human - immunology; Epitopes; Immunoenzyme Techniques; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Myocarditis - etiology; Myocarditis - immunology; Myocarditis - pathology; Myocardium - pathology; Neutralization Tests; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.67.3.589

Acute myocardial damage similar to that seen in human myocarditis occurs in BALB/c mice after infection with coxsackievirus B3 (CB3) or encephalomyocarditis virus (EMC). To investigate the role of antigen-specific T cells in the pathogenesis of this disorder, we compared CB3 disease expression in T cell-deficient, athymic nude (nu/nu) mice, in heterozygote (nu/+) mice with normal T cell function, and in nu/nu mice reconstituted with spleen cells from CB3-or EMC-infected nu/+ mice. Acute myocarditis occurred in both nu/nu and nu/+ mice. Severe myocarditis, however, developed only in nu/+ and nu/nu mice reconstituted with CB3-sensitized T cells, but not in those reconstituted with EMC-sensitized T cells. Myocardial virus titer and serum anti-CB3 antibody production were similar in nu/+ and nu/nu groups. Additionally, the presence of Thy 1.2 (pan T), Ly 1 (precursor of other T cell subsets), and Ly 2 (suppressor/cytotoxic T) positive cells was demonstrated in the myocardium in nu/+ and nu/nu mice reconstituted with CB3 -sensitized T cells, but not with T cells sensitized by another virus, EMC. These results indicate that immature but antigen-specific T cells play a role in the pathogenesis of ongoing myocarditis.