The immunosuppressive role of alpha-fetoprotein during pregnancy.

Cell-mediated and humoral immune responses were assessed in mice at mid-term (day 10) in pregnancy. A significant but selective suppression of the primary in vivo antibody (plaque-forming cell) response to SRBC was observed, with the most pronounced effect being on the gammaA response. Similar results were obtained for secondary in vitro antibody synthesis by antigen-primed spleen cells from pregnant mice, demonstrating the intrinsic nature of the inhibition. Pregnant mouse serum (PMS) was shown to suppress primary in vitro antibody synthesis, and the inhibitory effect was abrogated by the selective removal of alpha-fetoprotein (AFP) using affinity chromatography. Normal mouse serum became similarly suppressive in vitro when purified AFP of fetal origin was added to it in concentrations approximating that found in PMS. Spleen cells from pregnant mice showed a suppressed mitogenic response to phytohemagglutinin, a lowered response to concanavalin. A, and a normal response to lipopolysaccharide. In contrast, the allogeneic response of these animals as measured in the one-way mixed lymphocyte culture was enhanced. PMS suppressed both allogeneic and mitogen-induced lymphocyte transformation by spleen cells from nonpregnant mice, and the effect was eliminated by the selective removal of AFP. These findings indicate an important functional role for AFP in normal embryological development.