Natural killer cells in the pathogenesis of preeclampsia: a double-edged sword

Objective: To investigate the relationship between natural killer (NK) cells, extravillous trophoblast cells (EVTs) and vessel remodeling in early human pregnancy, and the association between NK cells and preeclampsia (PE) in late human pregnancy. Methods: Human decidual tissues from women with normal pregnancies were collected and examined for the relationship of NK cells with uterine vessel remodeling using immunohistochemistry. Percentages of peripheral blood NK (pNK) and decidual NK (dNK) cells and the levels of intracellular interferon (IFN)-gamma, perforin and granzyme B in normal pregnancies, late-onset and early-onset PE were analyzed using flow cytometry. Cytolytic functions of dNK cells from normal and PE pregnancies were examined. Effects of conditioned medium (CM) of dNK cells from normal and PE pregnancies on first trimester trophoblast invasion and migration were tested. Results: In early pregnancy samples (9-13 weeks of gestation), we noted moderate vessel remodeling with abundant perivascular NK cells but a limited number of surrounding EVTs. The numbers of both human pNK cells and dNK cells and intracellular interferon (IFN)-gamma, perforin and granzyme B production were significantly higher in PE compared with normal pregnancies at the time of delivery for both early- and late-onset disease. dNK cells from PE pregnancies not only killed first trimester trophoblasts but also inhibited their invasion and migration when compared to normal controls. Conclusion: Our results suggest that NK cells, in conjunction with EVTs, may play an important role in controlling uterine SA remodeling at the early stages of vessel remodeling, but they contribute to the pathogenesis of PE in late pregnancy.