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Journal of Virology, June 1999, p. 4689-4695, Vol. 73, No. 6
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

S. A. Huber,* J. Kupperman, and M. K. Newell

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.Ealpha 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 gamma delta T-cell receptor were found in male and testosterone-treated male and female mice. In vivo depletion of gamma delta + 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 gamma delta + 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.


Journal of Virology, June 1999, p. 4689-4695, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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