Adaptive Immunity in Pregnancy

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Background

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 and 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 susceptible to 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. T cell-mediated immune responses can drive activation of allograft rejection or tolerance mechanisms, promoting pregnancy failure or fetal survival respectively.

Therefore, the quality and strength of the adaptive immune response are critical to a 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.

This Research Topic calls for Original Research articles, Reviews, Clinical Trials, Methods, and Perspectives focusing on but not restricted to:

1. Defining the biological pathways through which the T cell response is developed during pregnancy, and the key intrinsic and external regulatory events and factors that regulate it.
2. Defining the most relevant T cell subpopulations during healthy pregnancy, and changes in these subsets in women with fertility and gestation disorders.
3. Defining the critical antigens which drive the T cell activation necessary to establish regulatory T cell response.
4. Defining the biological and clinical significance of transplacental bidirectional transfer of immune cells between mother and fetus (microchimerism).
5. Defining the adaptive immune response during pregnancy in women with autoimmune disease or allergy, and its role in pregnancy outcomes.
6. Developing rigorous clinical trials in which T cells may be a rational target for developing both preventative strategies and treatment interventions in fertility and pregnancy conditions. Approaches include pregnancy planning and preconception care to boost immune function, and potentially pharmacological interventions to modulate the adaptive immune response.
7. Developing informative and cost-effective diagnostic tests for T cell function that can be used before conception or during early pregnancy in at-risk women.

Keywords: T cells, Pregnancy, Abortion, APCs, Fertility

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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