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.E alpha mice. This gender difference in disease sus ceptibility correlates with selective induction of CD4(+) Th1 (gamma interf eron-positive) cell responses in animals with testosterone, whereas estradi ol promotes preferential CD4(+) Th2 (interleukin-il positive [IL-4(+)]) cel l responses. Differences in immune deviation of CD4(+) T cells cannot be ex plained by variation in B7-1 or B7-2 expression. Infection significantly up regulated both molecules, but no differences were detected between estradio l- and testosterone-treated groups. Significantly increased numbers of acti vated (CD69(+)) T cells expressing the gamma delta T-cell receptor were fou nd in male and testosterone-treated male and female mice. In vivo depletion of gamma delta(+) cells by using monoclonal antibodies inhibited myocardit is and resulted in a shift from a Th1 to Th2 response phenotype. Taken toge ther, our results indicate that testosterone promotes a CD4(+) Th1 cell res ponse and myocarditis by promoting increased gamma delta(+) cell activation .