Hormonal regulation of CD4(+) T-cell responses in coxsackievirus B3-induced myocarditis in mice.
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 gammadelta T-cell receptor were found in male and testosterone-treated male and female mice. In vivo depletion of gammadelta+ 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 gammadelta+ cell activation.
Huber
S A
SA
Departments of Pathology and Medicine, University of Vermont, Burlington, Vermont 05405, USA. shuber@salus.med.uvm.edu
Kupperman
J
J
Newell
M K
MK
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology*; D029822:Enterovirus B, Human; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013739:Testosterone / Q000494:pharmacology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D013739:Testosterone; D004958:Estradiol