Sa. Huber et al., Hormonal regulation of CD4(+) T-cell responses in coxsackievirus B3-induced myocarditis in mice, J VIROLOGY, 73(6), 1999, pp. 4689-4695
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
.