T cell-mediated immune response enhances the severity of myocarditis in secondary cardiotropic virus infection in mice.
In this report, we showed that a previous enterovirus exposure in ordinary mice with normal T cell function, but not in T cell-deficient mice, can influence development of myocardial inflammation with a second virus exposure. Inoculation of 4-week-old male BALB/c-nu/+ (euthymic and normal T cell function) mice with amyocarditic Coxsackie virus B1 (CB1), followed by inoculation 28 days later with myocarditic variant of Coxsackie virus B3 (CB3-m) resulted in more intense myocardial inflammation and injury than was seen in BALB/c-nu/+ inoculated with CB1, followed by inoculation with non-enterovirus, i.e., encephalomyocarditis virus (EMC) or influenza A virus and in age-matched BALB/c-nu/+ mice secondary inoculated with CB3-m alone. In contrast, this phenomenon of the enhancement of the severity of myocarditis by a secondary CB3-m inoculation was not seen in BALB/c-nu/nu (athymic and T cell- deficient) mice. Interestingly, inoculation of BALB/c-nu/+ mice with CB1, followed by inoculation 28 days later with another amyocarditic variant of Coxsackie virus B3 (CB3-o), resulted in more severe myocarditis than was seen in age-matched BALB/c-nu/+ mice secondary inoculated CB3-o alone. Myocardial-activated T cells and elevated serum interleukin-6 were involved in the exacerbation of the disease during the reinfection. T cell-mediated immune responses to a conserved antigenic epitope among the enteroviruses may be involved in the exacerbation of myocardial inflammatory disease during a second enterovirus infection.
Kishimoto
C
C
The Department of Cardiovascular Medicine, Graduate School of Medicine, Japan. kkishi@kuhp.kyoto-u.ac.jp
Hiraoka
Y
Y
Takada
H
H
D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D029822:Enterovirus B, Human; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
D015850:Interleukin-6; D007371:Interferon-gamma