Uterine natural killer cells ace an “A” in education: NKG2A sets up crucial functions at the maternal-fetal interface

I argue here that reproduction was a driving force in the evolution of NK-cell education, which is set by interactions between inhibitory receptors and self MHC. Maternal lymphocytes also interact with allogeneic MHC on fetal trophoblast cells. How the maternal immune system accommodates the semi-allogeneic fetus is a fascinating question. But it may be the wrong question. Tissue lymphocytes, like uterine NK (uNK) cells, do not attack the mismatched fetus and its placenta. Instead, they help the local vasculature to accommodate changes necessary to nourish the fetus. Education of uNK cells, driven by the ancient CD94:NKG2A inhibitory receptor and self MHC, sets them up to deliver these key functions at the maternal-fetal interface. /112