Decidual natural killer (dNK) cells are distinct to peripheral blood NK cells with regard to both surface receptor expression and function. Decidual NK cells are predominantly CD56brightCD16-, are non-cytotoxic and are thought to function primarily through the secretion of cytokines. The role played by dNK cell inhibitory and activating receptors and secreted cytokines in the interaction of dNK with trophoblast, and therefore the indirect role of dNK in spiral artery (SA) remodelling, is unknown.
Uterine artery Doppler resistance index (RI) in the first trimester of pregnancy can be used as a proxy measure of the extent of remodelling of the SA. We have used this technique to isolate dNK cells from pregnancies with normal (normal RI) and impaired (high RI) SA remodelling. The phenotype of these dNK cells was compared by examination of expression of activating and inhibitory receptors on dNK cells. The function of dNK cells from normal and high RI pregnancies was investigated by assessing trophoblast invasion, chemotaxis and explant outgrowth in response to dNK cells secreted factors.
A greater percentage of dNK cells from normal RI pregnancies expressed the receptors ILT2 (p<0.01) and KIR2DS/L1,3,5 (p<0.05) as compared to dNK cells from high RI pregnancies. This may have implications for dNK interactions with trophoblast expressing the ligands HLA-G and HLA-C, which bind to ILT2 and KIR2DS/L1,3,5,respectively. Additionally, chemo-attraction of trophoblast and trophoblast outgrowth from placental explants induced by dNK cell CM was significantly greater from dNK cells isolated from normal compared to high RI pregnancies (p<0.05). Collectively, these results indicate that impaired dNK cell-trophoblast interactions may consequently lead to poor placentation.