Apoptosis in coxsackievirus B3-induced myocarditis and dilated cardiomyopathy.
Group B coxsackieviruses (CVB), which infect the myocardium, cause myocarditis and dilated cardiomyopathy. However, not all infections of the myocardium result in disease. In the mouse model, CVB infection stimulates autoimmune T cell response to cardiac antigens, and these autoimmune effectors cause myocyte necrosis and cardiomyopathy. Induction of pathogenic autoimmunity depends upon CD4+ Th1 (interferon-gamma positive) cells while Th2 (IL-4 positive) cell responses promote disease resistance. T lymphocytes expressing the gamma-delta T cell receptor (gamma delta +) constitute up to 12% of the inflammatory cells in the heart and are crucial to maintaining a dominant Th1 response phenotype. gamma delta + lymphocytes modulate T cell responses by selectively lysing CD4+ Th2 cells. Th1 cells are not killed by gamma delta + cells. Lysis requires direct cell:cell interaction between the gamma delta + cell and CD4+ Th2 target and is most likely mediated through Fas:FasL interaction. These studies demonstrate a novel mechanism for immune modulation of cytokine responses in vivo.
Huber
S A
SA
Department of Pathology, University of Vermont, Burlington 05405, USA. shuber(a)salus.uvm.edu
Budd
R C
RC
Rossner
K
K
Newell
M K
MK
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology*; D029822:Enterovirus B, Human; D006801:Humans; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016692:Receptors, Antigen, T-Cell, gamma-delta