The outcome of coxsackievirus B3-(CVB3-) induced myocarditis is influenced by the cellular immune status.
Mice develop a marked age-related susceptibility to myocardial coxsackievirus B3 (CVB3) infections. The lesions observed in mice resemble closely those seen in the human disease. Experimental murine models of CVB3-induced myocarditis have shown that both, host and viral genetic factors, can influence susceptibility to the infection as well as the persistence and progression of the disease. Recently, we have shown that CD4 T cell-deficient MHC Class II knockout mice develop a strong fibrosis with virus persistence in the heart tissue and without production of neutralizing antibodies. To examine the role of CD4+ T cells and especially the role of the T helper 1 cell response for the outcome and pathogenesis of CVB3-induced myocarditis in more detail, 2 different mouse strains with identical genetic background (H-2b) were infected with CVB3-Mü/J (Nancy strain). Immunocompetent C57BL/6 mice and mice with targeted disruption of interleukin (IL-)4 gene (IL-4-/- mice) developed a severe acute myocarditis on day 7 post infection (p.i.). The CVB3-induced inflammation was cured until the 21st day p.i. in hearts of C57BL/6 mice. IL-4-/- mice with insufficient T helper-2 cell immune response developed a severe myocardial damage between day 7 and 21 p.i. with prolonged virus persistence in the heart tissue. Therefore, we suggest that despite an obvious normal T helper-1 cell cytokine pattern, IL-4-/- mice are more susceptible to long-term heart muscle injuries after infection with CVB3.
Leipner
C
C
Institut für Virologie, Klinikum der Friedrich-Schiller Universität, Jena, Germany. carola.leipner@uni-jena.de
Grün
K
K
Borchers
M
M
Stelzner
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D003384:Coxsackievirus Infections / Q000175:diagnosis / Q000276:immunology*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology; D011379:Prognosis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology
D015847:Interleukin-4