Fetal histocompatibility antigens and maternal immune responses.

Information on the antigenic status of the fetus and placenta and the nature of the maternal alloimmune responses in pregnancy is essential for an understanding of the factors responsible for the survival of the fetus as an intrauterine allograft. Although minor histocompatibility antigens are expressed from the earliest stages of preimplantation embryonic development in the mouse the paternally inherited Class I antigens of the major histocompatibility complex are absent from both fetal and surrounding trophoblastic tissues until the mid-gestation period. In the definitive placenta, the spongiotrophoblast, a major subpopulation of trophoblast in direct contact with maternal blood and uterine tissue, expresses these MHC antigens and is potentially susceptible to immune attack. The maternal alloimmune response is extremely restricted. Antibody is detectable only in females of an H-2b haplotype, only after a second allogeneic mating, and exhibits little or no complement-fixing activity, There is no detectable generation of cytotoxic T cells. Placental and fetal tissue inoculation experiments indicate that the deviated response in pregnancy is mediated at the placental level. The failure of an experimentally induced state of hyperimmunity to prejudice the course of pregnancy is considered to be due to the immunoregulatory effect of non-antigen-specific maternal serum factors.