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  • Title: Sex steroids induce apoptosis of CD8+CD4+ double-positive thymocytes via TNF-alpha.
    Author: Guevara Patiño JA, Marino MW, Ivanov VN, Nikolich-Zugich J.
    Journal: Eur J Immunol; 2000 Sep; 30(9):2586-92. PubMed ID: 11009092.
    Abstract:
    T cell production by the thymus, thymic size, cellularity and output all decrease drastically after puberty. Among the candidates that may mediate this decrease are the sex steroids: hypersecretion or pharmacological administration of these hormones has long been known to induce thymic hypocellularity, and their depletion yields thymic hypercellularity. Here we show that a typical sex steroid, testosterone, specifically targets CD8+CD4+ double-positive (DP) thymocytes for apoptosis via TNF-alpha. Anti-TNF-alpha monoclonal antibodies abrogated testosterone-induced DP apoptosis, and TNF-alpha-/- DP thymocytes were largely resistant to testosterone-mediated apoptosis in vivo. Testosterone accomplished this effect by upregulating TNF-alpha production and by simultaneously sensitizing DP thymocytes to TNF-alpha. Thus, TNF-alpha is the critical mediator of sex steroid-induced apoptosis in thymocytes, and its manipulation should provide a point of intervention to modulate T cell production in sex hormone disorders.
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