Adaptive Immunity in Pregnancy

One of the most remarkable features of reproductive biology is the fact that a healthy woman can successfully carry her genetically disparate conceptus to full term, without immune rejection. The juxtaposition of the placenta and decidua creates what is referred to as the ‘fetal-maternal interface’, where placental trophoblasts of fetal origin and maternal uterine lymphocytes come into close contact. Due to the presence of paternal class I HLA-C molecules on trophoblasts, the conceptus can be considered to resemble a semi-allograft. Conceptus-derived and placental-derived antigens act to both prime maternal T cells and render the conceptus potentially susceptible to inflammatory effector activity or T cell-mediated attack. After presentation of paternal alloantigens by maternal antigen presenting cells (APCs), the maternal alloantigen-specific T cells proliferate and secrete cytokines, responsible for the activation of allograft rejection or tolerance mechanisms, respectively promoting pregnancy failure or fetal survival. Therefore, the quality and strength of the adaptive immune response is critical to healthy pregnancy. There is accumulating information that imbalance in the numbers, phenotypes and functional activity of T cell subsets can adversely impact fertility and pregnancy health. Predominant Th1, Th17 and Th17/Th1 immunity and decreased Th2, Th17/Th2 and Treg cells are associated with recurrent pregnancy loss (RPL) of fetuses with normal fetal chromosomal content. Various subsets of T cells are essential for pregnancy tolerance and interact in networks with innate immune cells to counteract inflammation and promote robust placental development. In fact, immune cells that populate the decidua are specialized not only to minimize events that might evoke conceptus attack, but also to foster placental development and function and to combat infections during pregnancy. In addition, T cells are commonly perturbed in late gestation disorders including preeclampsia, fetal growth restriction and spontaneous preterm birth. There is some evidence that T cell disturbances precede the onset of symptoms and contribute to disease pathophysiology through events around the time of implantation and early placental development. In this Research Topic we welcomed six original articles and four review articles, which discuss the role of novel immunosuppressive cells and molecules regulating fetal tolerance and development.