Estradiol prevents and testosterone promotes Fas-dependent apoptosis in CD4+Th2 cells by altering Bcl 2 expression

Coxsackievirus B3 (CVB3) induces myocarditis in male BALB/c mice. Female mi ce are resistant to viral myocarditis, except in the third trimester of pre gnancy and postpartum. Cardiac damage is mediated by T lymphocytes activate d during virus infection. Th1 (interferon-gamma+) cell responses promote ca rdiac injury, while disease resistance correlates to preferential activatio n of Th2 (interleukin-4+) cell responses. CVB3-specific Th1 and Th2 cell cl ones were established, treated with between 0 and 100 ng/ml 17 beta estradi ol and 4-androsten-17 beta-ol-one (testosterone) for two days, Cr-51-labele d and cultured on FasL-transfected 3T3 cells to determine susceptibility to Fas-dependent apoptosis. Testosterone treatment enhanced Th2 cell lysis wh ile estradiol treatment was protective. Staining of Th2 cells for Bcl 2, an anti-apoptotic factor, indicates that Bcl 2 expression increased in these cells with estradiol but decreased with testosterone exposure. Hormone-indu ced changes in Bcl 2 expression likely explain the selective survival of Th 2 cells in females and prevention of viral myocarditis.