Progesterone and estradiol suppress human mononuclear cell cytotoxicity

Fetal trophoblast is generally resistant to lysis by cytotoxic cells. We hypothesized that progesterone and estrogens secreted by the trophoblast act at the choriodecidual interface where they are present in high concentrations to provide a local, paracrine immunosuppressive effect on cellular cytotoxicity. Using peripheral blood mononuclear cells as effector cells in a cytotoxicity assay, we evaluated the effects of progesterone, estrone, estradiol and estriol, either alone or in combination, on cellular cytotoxicity. Both progesterone and estradiol suppressed cytotoxicity in a dose-dependent manner. Estrone, estriol, pregnenolone and cholesterol had no effect. A synergistic suppression of cytotoxicity was observed when estrone, estradiol, estriol and progesterone were combined. We speculate that trophoblast production of progesterone and estradiol may be an important local immunosuppressive mechanism contributing to fetal survival.