HOMOGRAFT IMMUNITY IN PREGNANCY SURVIVAL RATES IN RABBITS BORN OF OVA TRANSPLANTED INTO SENSITIZED MOTItERS BY JONATHAN T. LANMAN, M.D., LLEWELLYN HEROD, A~D

The resemblance of the mammalian fetus to a homograft has raised the question as to why it is not rejected by the mother in the manner of a homograft. That portion of the fetus' genetic makeup which is derived from the father should afford sufficient histoincompatibility to evoke an immunologic response in the mother. I t was at one time suggested that the onset of labor might result from the development of maternal homograft immunity against her fetuses, with their subsequent rejection. There are, however, various objections to this concept. For example, strains of animals inbred to the point of histocompatibility would on this basis be incapable of delivering their young, but no differences in gestation time have occurred in highly inbred strains of mice. In adclifton, various studies both in animals (1-3) and man (4) have not only failed to demonstrate the appearance of maternal homograft sensitization against the fetuses but on the contrary have shown that a degree of tolerance to paternal strain tissues may develop in the mother as a result of one or more pregnancies. Although homograft sensitization of the mother does not appear to occur naturally, the mother can be experimentally sensitized against her fetuses. A degree of incompatibility can be achieved by grafts made before pregnancy from a prospective father to the mother, and subsequent transplants of tissue from the fetuses or offspring to the mother show the anticipated accelerated rejection (5). Despite such maternal sensitization, apparently normal pregnancies are possible. More recently, we have carried out experiments (6) in which, by using transplanted eggs, sensitization of a mother against both maternal and paternal components of the fetus' genetic makeup can be achieved. Under these conditions also, apparently normal young are born after a normal gestation time. Studies of this type demonstrate that a normal pregnancy is possible in the face of maternal sensitization against her fetuses. They do not, however, reveal whether some of the fetuses had been destroyed, leaving as survivors only a selected population of perhaps less incompatible fetuses. We have therefore carried out a series of experiments in which a rabbit sensitized by skin grafts against both members of one breeding pair was later simultaneously im-