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Journal of Virology, June 1999, p. 4689-4695, Vol. 73, No. 6
Departments of Pathology and Medicine,
University of Vermont, Burlington, Vermont 05405
Received 11 December 1998/Accepted 1 March 1999
Coxsackievirus B3 infection causes significant cardiac inflammation
in male, but not female, B1.Tg.E
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Hormonal Regulation of CD4+ T-Cell
Responses in Coxsackievirus B3-Induced Myocarditis in Mice
mice. This gender difference in
disease susceptibility correlates with selective induction of
CD4+ Th1 (gamma interferon-positive) cell responses in
animals with testosterone, whereas estradiol promotes preferential
CD4+ Th2 (interleukin-4 positive [IL-4+])
cell responses. Differences in immune deviation of CD4+ T
cells cannot be explained by variation in B7-1 or B7-2 expression. Infection significantly upregulated both molecules, but no differences were detected between estradiol- and testosterone-treated groups. Significantly increased numbers of activated (CD69+) T
cells expressing the 
T-cell receptor were found in male and
testosterone-treated male and female mice. In vivo depletion of

+ cells by using monoclonal antibodies inhibited
myocarditis and resulted in a shift from a Th1 to Th2 response
phenotype. Taken together, our results indicate that testosterone
promotes a CD4+ Th1 cell response and myocarditis by
promoting increased 
+ cell activation.
*
Corresponding author. Mailing address: Department of
Pathology, University of Vermont, 55A South Park Dr., Colchester, VT 05446. Phone: (802) 656-8944. Fax: (802) 656-8965. E-mail:
shuber{at}salus.med.uvm.edu.
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