Immunology of human placental implantation: clinical implications of our current understanding

Abstract

In the early 1950s, Medawar proposed the concept of "the fetus as an allograft". Since then, the immunological relationship between the mammalian fetus and its mother during pregnancy has been considered to be similar to that between a transplanted allograft and its recipient. Because of this analogy, it has been assumed that implantation of the fetal placenta in the uterus would similarly be controlled by a maternal immune response mediated by T cells recognizing paternally derived alloantigens expressed by the placenta. Surprisingly, recent evidence suggests that implantation might predominantly involve a novel allogeneic recognition system based on natural killer cells rather than T cells. The cellular and molecular basis of this local immune interaction between the fetal placenta and maternal uterus is now the focus of intense research interest. Because aberrant implantation can cause a variety of clinical problems including miscarriage, intrauterine growth retardation and pre-eclampsia, an understanding of the immunological mechanism by which this process is controlled could lead to the development of regimes to treat these important obstetric conditions.