Pregnancy-induced NK cells of importance to gravidity and preeclampsia

Immunological changes induced by a woman's first pregnancy in controls and in cases of preeclampsia, which is more frequent and often a more severe complication in primigravid women, were investigated. Decidual natural killer (NK) cells are important for placentation and interact with HLA Ib molecules on extravillous trophoblast cells through specific receptors. In a clinical study part, we identified an increase in the CD56brightCD16-ILT2+ NK subpopulation in peripheral blood in multigravid women compared with primigravidae. Higher levels of decidual-like CD56brightCD16- NK cells in primi- versus multigravid women were observed. The cytotoxic CD56dimCD16+ NK cells and CD56+ NK cells were more abundant in primigravid preeclampsia cases. Other discrepancies in NK subpopulations in preeclampsia according to gravidity were identified in comparison to control pregnancies. The frequency of CD56brightCD16+ NK cells were significantly lower in multigravid control women compared with primigravidae; this was not the case for preeclampsia indicating less induction of CD56brightCD16- NK cells in primigravid women, who develop preeclampsia. Studies of the mechanisms that induce decidual-like NK cells were performed with a human trophoblast-derived cell model with the choriocarcinoma cell line JEG-3 expressing HLA-G. We showed that IL-15 and co-culture with immune cells induce decidual-like CD56brightCD16- NK cells expressing the ILT2 receptor. NK cytotoxicity and CD107a+ degranulation were reduced after such priming. The findings support the development of less cytotoxic NK cells at the fetal-maternal interface of importance for "memory" in subsequent pregnancies and in preeclampsia.