Are CD57+ natural killer cells really important in early pregnancy failure?
ABSTRACT The aim of this study was to compare the CD57+ Natural Killer (NK) cell counts in normal pregnancies and in cases grouped according to different types of early pregnancy failure.
A prospective case control study which was set in Baskent University Faculty of Medicine, Obstetrics and Gynecology Department. A total of 119 women whose pregnancies ended in the first trimester were divided into elective pregnancy termination, incomplete miscarriage, intrauterine demise, ectopic pregnancy and recurrent pregnancy loss groups. CD57+ NK cells were stained and counted in the histologic preparations of the decidua in all of these groups.
CD57+ NK cell counts were 2.14+/-1.42 in control, 2.24+/-1.92 in incomplete miscarriage, 1.82+/-1.34 in intrauterine demise, 2.54+/-1.80 in ectopic pregnancy and 3.42+/-2.15 in recurrent pregnancy failure group. There were no statistically significant differences between the control group and the other four groups with respect to the CD57+ NK cell counts.
This study suggests that CD57+ NK cell count is not associated with early pregnancy failure.
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ABSTRACT: The endocrine system and the immune system interact closely during implantation and maintenance of pregnancy. One of the most striking examples of this communication is at the level of the decidua (endometrium of pregnancy). Here, under the influence of sex steroids, there is a dramatic increase of a unique population of lymphocytes, the uterine natural killer (uNK) cells, in early pregnancy. These cells derive predominantly from a subset of peripheral blood NK cells, which under hormonal influence gets recruited to the uterus. In mice, uNK cells play an important role in the development of placental vasculature. The role of these cells in human pregnancy is still not definitively established; however, they are believed to promote placental and trophoblast growth and provide immunomodulation at the maternal-fetal interface. In contrast to their presumptive role in the maintenance of a healthy pregnancy, uNK cells and peripheral NK cells are dysregulated in unexplained recurrent pregnancy loss. Herein, we review NK cell populations, their changes in number and function in altered endocrine environments during the menstrual cycle and pregnancy, the current data on their potential role in unexplained recurrent pregnancy loss, and mechanisms for potential therapies targeted to NK cell function for this enigmatic disorder.Endocrine Reviews 03/2005; 26(1):44-62. · 14.87 Impact Factor
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ABSTRACT: For several years, reproductive immunology has been dominated by the 'Th1/Th2' hypothesis, in which the fetus avoids maternal T-cell rejection through a bias towards T-helper (Th)2 cytokine production. The discovery that normal pregnancy is a controlled state of inflammation, at an early stage at the implantation site and also later systemically, has challenged this concept, as has the finding that the predominant immune interactions in the decidua are between the placental trophoblast and maternal natural killer (NK) cells instead of T cells. Here, we extend this concept to the interaction between the trophoblast and NK cells in the maternal circulation. We suggest novel ways in which the trophoblast might stimulate the maternal systemic inflammatory response, and how dysfunctional NK-cell activation could result in the maternal syndrome of pre-eclampsia.Trends in Immunology 10/2006; 27(9):399-404. · 9.49 Impact Factor
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ABSTRACT: Changes in the immune environment in the endometrium are believed to be important for successful implantation and maintenance of pregnancy. We have previously investigated global gene profiling in human endometrium during the window of implantation by oligonucleotide microarray technology, and analysis of these data underscore the regulation of a group of immune-related genes. The present study was therefore conducted to examine the pattern of expression and regulation of these genes including decay accelerating factor (DAF), indoleamine 2,3 dioxygenase (IDO), interleukin-15 (IL-15), IL-15 receptor alpha subunit (IL-15Ralpha), interferon regulatory factor-1 (IRF-1), lymphotactin (Lpn), natural killer-associated transcript 2 (NKAT2) and NKG5 in secretory and proliferative human endometrium. Endometrial biopsies were obtained from normally cycling women in the late proliferative and mid-secretory phase of the menstrual cycle. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analysis were used to determine the expression and regulation of these genes in secretory and proliferative human endometrium. Cellular localization of NKG5, Lpn and IDO by in situ hybridization in secretory-phase endometrium was also examined. Semi-quantitative RT-PCR and Northern blot results demonstrate that there is a coordinated upregulation of this group of genes during the window of implantation. We demonstrate the upregulation of immune-related genes IL-15Ralpha, Lpn and NKG5 in secretory versus proliferative human endometrium. We also demonstrate a similar upregulation in secretory endometrium of other immune-related genes, viz, DAF, IDO, IL-15, IRF-1 and NKAT2. The functions of these genes include stimulation of proliferation of uterine natural killer (uNK) cells, inhibition of cytolytic activity of uNK cells, inhibition of cell growth of T cells and other pathogens and inhibition of the classical complement pathway. Upregulation of these immune-related genes in the window of implantation suggests their role during the process of implantation and in immune tolerance of the implanting conceptus.American journal of reproductive immunology (New York, N.Y.: 1989) 11/2004; 52(4):244-51. · 3.32 Impact Factor