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Accumulation of Uterine CD16(−) Natural Killer (NK) Cells: Friends, Foes, or Jekyll-and-Hyde Relationship for the Conceptus?

Human cycling endometrium and early pregnant decidua are infiltrated by a unique lymphocyte subset of CD16(−) natural killer (NK) cells, which are minor cells in circulating blood and other organs. The number of uterine (u) CD16(−) NK cells rises sharply after ovulation. If pregnancy occurs, uCD16(−) NK cells increase further in number, but are shed during the menstrual period. uCD16(−) NK cells have the potential to produce cytokines and growth factors that play important roles in embryo implantation and placentation, but they are armed with cytolytic cytoplasmic granules. In the mid-secretory phase endometrium of women with recurrent miscarriages, dense accumulations of uCD16(−) NK cells also occur, like those seen in first-trimester decidua of uncomplicated pregnancies. This finding complicates understanding the exact roles of these NK cells at implantation sites. uCD16(−) NK cells are likely to be a mixture of indigenous endometrial NK cells and immigrant NK cells from the circulation. However, it is not yet known if NK cells from these two different origins display similar or unique characteristics. In this review, the potential underlying mechanisms for accumulation of uCD16(−) NK cells in uncomplicated pregnancies and in pathological pregnancies, especially recurrent miscarriages, are discussed.