Homograft immunity in pregnancy. The placental transfer of cytotoxic antibody in rabbits.

The mammalian fetus affixed to the uterine wall in some ways resembles a homograft, but maternal homograft immunity even when specifically directed against her fetuses fails to destroy them. The placental barrier appears to be critical in protecting the fetus against maternal immunologic attack. In order to evaluate the means by which it affords protection, we have measured in rabbits the transfer of cytotoxic antibody from mother to fetus. When the offspring were not the specific targets for maternal antibody, we found titers of cytotoxic antibody in the newborn animals at or near maternal levels in 16 of 18 cases (89 per cent), demonstrating the ability of this antibody to cross the rabbit placenta. When the offspring were appropriate targets for antibody, however, 11 of 18 newborn animals (61 per cent) had no demonstrable titer. We believe that in these latter cases, antibody had become fixed to antigenic sites and thereby had been removed from the fetal circulation. There was, however, no evidence of harm to any of the fetuses, either in survival (as demonstrated in a previous study) or in spleen or thymus weights or peripheral leukocyte and mononuclear cell counts. Cytotoxic antibody appears to reach the embryo early in gestation, since we found antibody in 8-day-old blastocyst fluid in each of 2 trials. We conclude that the fetus neither receives nor requires protection against cytotoxic antibody, and believe that fetal protection against maternal homograft immunity is afforded by a placental barrier to maternal mononuclear leukocytes.