© 1999 American Heart Association, Inc.
Integrative Physiology |
Susceptibility to Myocarditis Is Dependent on the Response of 
ß T Lymphocytes to Coxsackieviral Infection
From the Centre for Cardiovascular Research, The Toronto Hospital (M.A.O., K.A., W.-H.W., F.D., P.L.), and Ontario Cancer Institute and Amgen Institute and Departments of Medical Biophysics and Immunology (J.P., T.M.), University of Toronto, Toronto, Ontario, Canada.
Correspondence to Dr Peter P. Liu, Cardiology Research, The Toronto Hospital, EN12-324, 200 Elizabeth St, Toronto, Ontario, Canada, M5G 2C4. E-mail peter.liu{at}utoronto.ca
Abstract—Viral myocarditis is an
important cause of heart failure and dilated
cardiomyopathy. T lymphocytes are implicated in
myocardial damage in murine models of coxsackievirus B3 (CVB3)
myocarditis. We used knockout mice lacking CD4 (CD4-/-),
CD8 (CD8-/-), both coreceptors
(CD4-/-CD8-/-), or the T-cell receptor ß
chain (TCRß-/-) to address the contribution of T-cell
subpopulations to host susceptibility to CVB3 myocarditis. Severity of
disease was magnified in CD8-/- mice but attenuated in
CD4-/- mice, consistent with a pathogenic role
for CD4+ lymphocytes. Elimination of both CD4 and CD8
molecules from T lymphocytes by genetic knockout better protected mice
from myocarditis, demonstrating that both CD4+ and
CD8+ T cells contribute to host susceptibility. The same
benefit occurred in TCRß-/- mice, with prolonged
survival and minimal myocardial disease observed after CVB3 infection.
Elevated interferon-
and decreased tumor necrosis factor-
expression are associated with attenuated myocardial damage in
CD4-/-CD8-/- mice. These results show that
the presence of TCRß+ T cells enhances host
susceptibility to myocarditis. The severity of myocardial damage and
associated mortality are dependent on the predominant T-cell type
available to respond to CVB3 infection. One mechanism by which
CD4+ and CD8+ T-cell subsets influence the
pathogenesis of myocarditis may involve specific cytokine
expression patterns.
Key Words: myocarditis • coxsackievirus • T lymphocyte • cytokine • transgenic mice
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