Gender-dependent IL-12 secretion by APC is regulated by IL-10

Female SJL mice preferentially mount Th1-immune responses and are susceptib le to the active induction of experimental allergic encephalomyelitis. By c ontrast, young adult male SJL are resistant to experimental allergic enceph alomyelitis due to an APC-dependent induction of Th2 cells. The basis for t his gender-dependent differential T cell induction was examined by analysis of macrophage APC cytokine secretion during T cell activation. APC derived from females secrete IL-12, but not IL-10, during T cell activation. By co ntrast, APC derived from males secrete IL-10, but not IL-12, during T cell activation. Activation of T cells with APC derived from the opposite sex de monstrated that these cytokines were derived from the respective APC popula tions. Furthermore, inhibition of IL-10, but not TGF-beta, during T cell ac tivation resulted in the secretion of IL-12 by male-derived APC. APC from n aive male mice, in which IL-10 was reduced in vivo before isolation, also s ecrete IL-12, demonstrating altered APC cytokine secretion was due to an en vironment high in IL-10 before Ag encounter, Finally, APC derived from cast rated male mice preferentially secrete IL-12 during T cell activation. Thes e data demonstrate a link between gonadal hormones and APC activity and sug gest that these hormones alter the APC, thereby influencing cytokine secret ion during initial T cell activation.