Uterine NK Cells Ace an "A" in Education: NKG2A Sets Up Crucial Functions at the Maternal-Fetal Interface.

I argue in this review 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 tolerate the semiallogeneic fetus is a fascinating question. But it may be the wrong question. Tissue lymphocytes, like uterine NK cells, do not attack the mismatched fetus and its placenta. Instead, they help the local vasculature to tolerate changes necessary to nourish the fetus. Education of uterine NK 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.