title: Estradiol prevents and testosterone promotes Fas-dependent apoptosis in CD4+ Th2 cells by altering Bcl 2 expression.
abstract: Coxsackievirus B3 (CVB3) induces myocarditis in male BALB/c mice. Female mice are resistant to viral myocarditis, except in the third trimester of pregnancy and postpartum. Cardiac damage is mediated by T lymphocytes activated during virus infection. Th1 (interferon-gamma+) cell responses promote cardiac injury, while disease resistance correlates to preferential activation of Th2 (interleukin-4+) cell responses. CVB3-specific Th1 and Th2 cell clones were established, treated with between 0 and 100 ng/ml 17beta estradiol and 4-androsten-17beta-ol-one (testosterone) for two days, 51Cr-labeled and cultured on FasL-transfected 3T3 cells to determine susceptibility to Fas-dependent apoptosis. Testosterone treatment enhanced Th2 cell lysis while 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-induced changes in Bcl 2 expression likely explain the selective survival of Th2 cells in females and prevention of viral myocarditis.
authors.affiliation: Department of Pathology, University of Vermont, Burlington 05405, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Huber
authors.forename: J
authors.initials: J
authors.lastname: Kupperman
authors.forename: M K
authors.initials: MK
authors.lastname: Newell
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011817:Rabbits; D013739:Testosterone / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology; D018418:Th2 Cells / Q000187:drug effects* / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D013739:Testosterone; D004958:Estradiol