Natural mechanisms for evading graft rejection: the fetus as an allograft

Most primitive multicellular animals mount allogeneic immune responses to protect themselves from invasion by foreign organisms. The reproductive success of eutherian mammals, in which the maternal immune system is in direct contact with the semi-allogeneic fetus, depends on the ability to control allogeneic immune responses. Multiple, overlapping mechanisms exist to prevent maternal allogeneic immune responses towards the fetus while maintaining the capacity to mount a defense against infectious organisms. The formation of an anatomical barrier between mother and fetus, lack of maternal immune responsiveness, and a lack of expression of allogeneic molecules by the fetus have been proposed as mechanisms to account for the lack of fetal rejection during pregnancy. These mechanisms have helped us begin to understand how rejection of the fetus is avoided; however, these mechanisms do not completely explain how the fetus evades the maternal immune system. Site-specific suppression, in which maternal immune responses are controlled locally at the maternal- fetal interface, plays a fundamental role in controlling maternal allogeneic immune responses. Stem cells, both adult and embryonic, might use mechanisms similar to those of the fetus to avoid rejection. Future discoveries in the field of reproductive immunology will help us understand not only immune regulation during pregnancy, but also how immune responses towards organ and cellular transplants might be controlled.