Increased peripheral blood-activated NK cell counts are associated with increased risk of miscarriage and failed in vitro fertilization treatment. However, assessment of activated peripheral NK cells in normal and pathological pregnancies beyond implantation and early miscarriage has not been described. Total CD69 expressing NK cells counts were measured by flow cytometry in healthy women with singleton pregnancies, including 45 at 11+6–13+6 weeks’ gestation, 46 at 20+0–22+4 weeks, and 42 at 31+6–33+5 weeks. The number of peripheral blood NK cells decreased, whereas the percentage of activated CD69 expressing NK cells increased from the first to the third trimester of pregnancy. This study shows the course of peripheral blood NK cells and activated CD69 expressing NK cells in uncomplicated nulliparous singleton pregnancies. This is a first step in understanding their implication in pathological pregnancies. 1. Introduction It is now accepted that for a normal pregnancy to occur, the maternal immune system must be rendered more tolerant towards the semiallogeneic fetus. The required changes must ultimately result in controlled modulation of the uterine natural killer (uNK) cells that represent the most abundant cell population at the fetomaternal interface. These cells play a critical role in implantation and particularly in vascular remodelling and trophoblast invasion [1, 2]. As such NK cells have a critical role in the healthy progression of the pregnancy by maintaining the balance between placental function and fetal requirements. NK cells are also found in the peripheral blood and like uNK cells, these may be recognized by the expression of cell surface markers. They are usually CD3 negative, but express CD16 and CD56. NK cells are subdivided, by the intensity of expression of CD56, into a + and + . Peripheral blood NK (pNK) cells are predominantly + , whereas uNK cells are predominantly + [3, 4]. The exact relationship between these two sub-groups of NK cells is unclear but it has been suggested that uNK migrates from the systemic vascular system [5, 6]. Importantly, however, the factors that regulate uterine and peripheral blood NK cells are likely similar. Thus assessing the level of activation of the peripheral blood NK cells gives information of the state of the uterine cells [7]. CD69 is one of the earliest specific markers of NK cell activation [8–10]. Activated NK cells release cytokines that activate other NK cells and the cellular immune system generally [10]. Elevated NK cell CD69 expression is associated with increased cytotoxicity and
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