Evaluation of Homing and Functions of Uterine Natural Killer Cells

Abstract

Uterine Natural Killer cells are the major lymphocyte population in the pregnant uterus in early gestation; outnumbering both T and B cells. The numerical expansion of uterine Natural Killer cells is thought to result from the expansion of preexisting progenitor cells resident to the uterus, recruitment of Natural Killer cells from the circulation, or a combination of both pathways. Uterine Natural Killer cells are capable of cytotoxic killing and express receptors that can recognize foreign paternal antigens. Therefore, it has been argued that uterine Natural Killer cell activation can lead to killing of fetal cells and abortion. However, fetal rejection by uterine Natural Killer cells does not occur in normal pregnancies and other functions for uterine Natural Killer cells have been proposed. These include: the regulation of maternal blood supply responsible for providing oxygen to the fetus, regulation of maternal blood pressure and, in species with invasive placentation, regulation of decidualization, the process of endometrial cell expansion and transformation during the menstrual cycle and during pregnancy. These cell functions juxtapose the concept that uterine Natural Killer cell activation is harmful to the fetus and offer a new perspective that uterine Natural Killer cells regulate functions unrelated to traditional transplantation immunology. In this dissertation, work is presented showing that uterine Natural Killer cells express molecules which regulate blood pressure and decidualization. Also presented are data supporting the hypothesis that the numerical increase of uterine Natural Killer cells is due to the recruitment of Natural Killer cells from the blood. These results support roles for uterine Natural Killer cells other than cytotoxic killing and advance the understanding of uterine Natural Killer cells as dynamic players that support pregnancy-associated biological processes unrelated to traditional understandings of immune surveillance.