The Mammalian Fetus: Nature's (Almost) Perfect Allograft

In the human fetus, major histocompatibility antigens have been found in the early stages of pregnancy. For example, class I antigens have been detected in mesenchymal cells of the chorionic villi at 2–3 weeks by Sutton, Mason, and Redman, though they were weakly and sporadically expressed. It is found that both class I and II antigens are present in the thymic epithelial cells of seven-week-old fetuses. As fetal tissues appeared to possess antigens, a lack of paternal antigens was sought in the trophoblast—the fetal component of the placenta that is at the critical interface between the maternal blood and the fetus. It is doubtful that mammals would have survived and evolved, for the ready migration of maternal lymphocytes into the fetus would have opened up the possibility of widespread destruction of fetuses by an immunologic response against paternally inherited antigens. The trophoblast is an uninterrupted layer of fetal origin and it is the ultimate frontier between the maternal and fetal blood circulation in many mammalian species. Much attention has been focused on it, for a lack of paternally inherited histocompatibility antigens would explain the failure of maternal blood cells to be activated against the fetus.