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Uterine NK cells: active regulators at the maternal-fetal interface
Ashley Moffett, Francesco Colucci
Ashley Moffett, Francesco Colucci
Published May 1, 2014
Citation Information: J Clin Invest. 2014;124(5):1872-1879. https://doi.org/10.1172/JCI68107.
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Uterine NK cells: active regulators at the maternal-fetal interface

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Abstract

Pregnancy presents an immunological conundrum because two genetically different individuals coexist. The maternal lymphocytes at the uterine maternal-fetal interface that can recognize mismatched placental cells are T cells and abundant distinctive uterine NK (uNK) cells. Multiple mechanisms exist that avoid damaging T cell responses to the fetus, whereas activation of uNK cells is probably physiological. Indeed, genetic epidemiological data suggest that the variability of NK cell receptors and their MHC ligands define pregnancy success; however, exactly how uNK cells function in normal and pathological pregnancy is still unclear, and any therapies aimed at suppressing NK cells must be viewed with caution. Allorecognition of fetal placental cells by uNK cells is emerging as the key maternal-fetal immune mechanism that regulates placentation.

Authors

Ashley Moffett, Francesco Colucci

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Figure 1

Maternal immune response to fetus and placenta.

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Maternal immune response to fetus and placenta.
The maternal immune syst...
The maternal immune system does not ignore the fetal allograft. Antibodies specific for paternally inherited Rhesus D antigen and for HLA molecules — or, rarely, T cells specific for mismatched minor histocompatibility antigens — are found in the maternal circulation. However, these T cells do not normally reach the fetus itself, as this is protected by several mechanisms, including the placental barrier. The uterine mucosa is in direct contact with the fetal placenta at the maternal-fetal interface. This is the major site where fetal placental cells (not the embryo proper) are directly in contact with maternal tissues. The decidua is a specialized tissue that is rich in uNK and myeloid cells and also contains maternal T cells, including effector T cells and Tregs. Although it appears clear that uNK cells have receptors that can interact with HLA-C molecules on invasive trophoblast cells at the interface, how effector T cells might interact with the trophoblast cells is unclear. Circulating in the maternal blood are antifetal antibodies and T cells together with fetal cells and trophoblast cells.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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