Chapter Thirty - NK cells and reproduction

Abstract

In humans, an unusual subset of natural killer (NK) cells accounts for approximately 70% of the leukocytes in the mucosal lining of the uterus in the secretory phase of the menstrual cycle and during the first trimester of pregnancy. These NK cells are CD56superbright CD16+ and contain cytotoxic granules. They express a variety of activating and inhibitory NK cell receptors including NKG2A, NKG2D, NKp46, and killer-cell immunoglobulin-like receptors (KIR). Despite the presence of killer cell receptors and cytotoxic granules, uterine NK cells are poorly cytotoxic. There is evidence to suggest that they can produce various cytokines and soluble growth factors. Through production of these factors, uterine NK cells may have a physiological role in maintenance and modification of the vasculature and in mediating trophoblast invasion. correlation between the presence and abundance of NK cells, the degree of decidualization and the depth and extent of trophoblast invasion seems to indicate that uNK cells somehow contribute to the regulation of normal placentation and trophoblast invasion. In humans, there is circumstantial evidence that uNK cells may play a role in the normal physiological processes of the menstrual cycle. This will be an important area to explore because, if NK cells can be shown to prevent mucosal breakdown, this will have therapeutic possibilities in women suffering from dysmenorrhoea, infertility and recurrent miscarriage. The evidence that uNK cells play an important role in the regulation of placentation is accumulating both from genetic and functional studies. It is likely that humans may have developed this particular function more extensively than other species because placentation is far more invasive in humans than in other primates or mice.