Origin, phenotype and function of human natural killer cells in pregnancy

During the early phases of pregnancy, natural killer (NK) cells are the predominant lymphoid cells in the human decidua. Here, rather than act as killers and/or drivers of inflammation, NK cells contribute to tissue building and remodeling and formation of new vessels due to the release of interleukin-8, vascular endothelial growth factor, stromal cell-derived factor-1 and interferon gamma-inducible protein-10. Here, we propose that the interaction of NK cells with CD14(+) myelomonocytic cells to promote induction of T regulatory cells plays a pivotal role in immunosuppression and tolerance towards the fetus allograft. Importantly, CD34(+) hematopoietic precursors are present in human decidua and may give rise to decidual NK cells. Defects in decidual NK cell generation, or in appropriate functional interactions with other cell types, could have major consequences for successful pregnancy.