The significance of the women's repertoire of natural killer cell receptors in the maintenance of pregnancy.

Large numbers of decidual natural killer (dNK) cells are in direct contact with the invading trophoblast and are considered to be important for pregnancy, since they can produce cytokines and other mediators involved in the control of trophoblast invasion, trophoblast differentiation, decidual artery remodeling and placental augmentation. The dNK cells are also the main candidate cells to attack trophoblast in cases of alloimmune abortions, where the fetus is 'rejected' by the pregnant woman. The function of NK cells is regulated by a balance between activating and inhibitory signals provided by their heterocladic receptor repertoire upon recognition of specific ligands, most of which are HLA molecules (HLA-C, HLA-G, HLA-E) expressed on invading trophoblast. It is a challenge to investigate abortions in regard to the receptors that dNK cells bear and the MHC molecules that the trophoblast expresses. Our studies in couples with recurrent spontaneous abortion as well as in random cases of abortion revealed that aborting women usually have a limited repertoire of inhibitory receptors of the KIR family (inhKIR), and that many of them lack inhKIRs specific for the fetal HLA-Cw antigens. We suggest that some spontaneous abortions are caused because of a limited maternal inhKIR repertoire and a lack of maternal inhKIR-fetal HLA-C epitope matching. Among the different interactions of NK receptors with their specific counterparts on trophoblast, the inhKIR-HLA-C interactions appear to be those mainly involved in the function of an NK cell-mediated allorecognition system in pregnancy.