Modification of immune function during pregnancy by products of the sheep uterus and conceptus

The preimplantation sheep conceptus produces several molecules that inhibit lymphocyte responses in vitro to mitogens or allogeneic cells, including prostaglandin E-2 and a lactosaminoglycan-containing glycoprotein of Mr 800,000-900,000. Additionally, the definitive placenta releases immunosuppressive factors when placed in culture. One of these is a heat- and protease-stable, carbohydrate-containing molecule released by explants of cultured fetal cotyledons. The pregnant uterus also produces molecules that alter lymphocyte responsiveness in vitro, including a dialysable, heat- and trypsin-stable factor and a high-molecular weight factor (Mr greater than 4 x 10(6]. An important regulator of uterine immune function is progesterone. This hormone can induce the production of uterine immunosuppressants such as seen during pregnancy and prolong the life of skin allografts placed in utero. Taken together, results suggest that the conceptus resides in an immunosuppressive environment throughout most of gestation, a situation that may be critical to maintenance of pregnancy.