The "Miracle" fetus: an excellent model for apoptotic cell-induced immune tolerance?

For several decades, people have wondered why pregnant mothers do not reject fetuses bearing allogeneic paternal antigens. Several hypotheses have been proposed, including a physical barrier between fetus and mother, immaturity of fetal antigens and temporary dormancy of the maternal immune system. Based on the "cell death immune recognition model," the author proposes a hypothesis that pregnancy tolerance is an active immune response of the maternal immune system, which is induced by apoptotic cells bearing paternal antigens. The primary steps in the induction of pregnancy tolerance are apoptosis of fetal cells and spermatozoa, phagocytosis of those dying/dead cells by maternal antigen presenting cells (APC), migration of APC to local lymph nodes, and antigen presentation and induction of regulatory T cells in local lymph nodes. The hypothesis outlined below will not only help us to understand how pregnancy tolerance is induced, but also provide novel strategies to develop clinical measures for patients with infertility or pregnancy-related disorders.