Zeitschrift für Immunbiologie

Natural Killer (NK) Cell Receptors and their Role in Pregnancy and Abortion

Abstract

Marigoula Varla-Leftherioti and Theodora Keramitsoglou

Existing data suggest that decidual Natural Killer Cells (dNK CD3-CD56brightCD16dim/-) are important in early pregnancy (local response to pathogens, control of trophoblast invasion, uterine vascular remodeling), while in ongoing pregnancy they contribute to the acceptance of the embryo through various immunoregulatory mechanisms. In the so-called alloimmune abortions, CD3-CD56brightCD16dim/-NK cells are decreased in favor of CD3-CD56dimCD16bright NK cells, which are toxic for trophoblast. Most of the activating and inhibitory receptors regulating dNK function belong to the highly polymorphic KIR (Killer Immunoglobulin-like) family. KIRs have as ligands the only HLA molecules expressed on extravillous cytotrophoblast (HLA-C, -E, -G). The interactions of maternal KIR receptors with fetal HLA-C molecules provide an immunogenetic allorecognition system. If inhibitory KIRs recognize their specific ligands, they inhibit dNK activation for trophoblast damage. Otherwise, dNK are allowed to develop anti-trophoblast activity. Given the differences in both the KIR repertoire and the HLA-C allotypes among unrelated individuals, each pregnancy presents a different combination of maternal KIR receptors on dNK and self and non-self HLA-C allotypes on trophoblast. Current studies provide evidence for differences between the combinations arising in successful pregnancies to those found in cases of abortions.