The expression of Th1- and Th2-related chemokine receptors in women with recurrent miscarriage: the impact of lymphocyte immunotherapy.
ABSTRACT Recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The aim of this study was to investigate the expression of T helper (Th)1- and Th2-related chemokine receptors on CD4(+) T helper and CD8(+) T cytotoxic (Tc) cells in RM and control subjects. The effects of lymphocyte immunotherapy on the balance of Th1/Th2 and Tc1/Tc2 chemokine receptors were further evaluated in RM women.
The expression of Th1-related (CCR5 and CXCR3) and Th2-related (CCR3 and CCR4) chemokine receptors on CD4(+) or CD8(+) T cells from RM women were analyzed and compared with controls using flow cytometry. The expression of chemokine receptors in RM women was also compared before and after lymphocyte immunotherapy.
The ratios of Th1/Th2 and Tc1/Tc2 chemokine receptors were higher in RM women compared to controls. The ratio of Th1/Th2 chemokine receptors was decreased in RM women after immunotherapy, while no significant change was identified in the Tc1/Tc2 after immunotherapy.
This study indicates the Th1 dominant immune responses in circulation of RM women compared to controls. Moreover, lymphocyte immunotherapy might influence pregnancy outcome via a shift in the balance of the Th1/Th2 chemokine receptors.
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ABSTRACT: Monocytes are precursors of macrophages and recruited to the uterus throughout pregnancy to perform important immunological functions. In this study, we hypothesized that pregnant women have reduced peripheral monocyte expression of chemokine receptors and alterations in PBMC responses to microbial stimuli as an adaption to pregnancy and that these changes are less pronounced in women with autoimmunity. We therefore investigated the chemokine receptor expression, migratory behaviour and responses to microbial stimulation of peripheral monocytes from pregnant women at parturition (n = 13) and from non-pregnant women (n = 9). In addition, we compared healthy pregnant women with women suffering from SLE (n = 5), a condition with pronounced systemic inflammation increasing the risk for pregnancy complications. We demonstrate that peripheral monocytes are affected by pregnancy with reduced percentages of CCR2+, CCR5+ and CXCR3+ monocytes of both classical (CD16−) and inflammatory (CD16+) subsets and that the trophoblast-secreted chemokine CCL2/MCP-1 recruited monocytes of both subsets in vitro. Further, PBMCs from pregnant women had a divergent response to microbial stimulation with lower CCL5/RANTES and higher CCL2/MCP-1 secretion compared with non-pregnant women. In addition, pregnant women had lower basal PBMC-secretion of CCL5/RANTES and higher basal secretion of IL-10 and CCL2/MCP-1. Interestingly, the women with SLE responded similar to pregnancy as did healthy women with lower percentages of CCR2+, CCR5+ and CXCR3+ monocytes. However, they had increased expression of CCR5 on CD16+ monocytes and heightened PBMC-secretion of CCL5/RANTES. In conclusion, our data indicate that monocyte chemokine receptor expression and the chemokine milieu during pregnancy are tightly regulated to support pregnancy.Scandinavian Journal of Immunology 01/2013; 77:200-212. · 1.88 Impact Factor
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ABSTRACT: The aim of this study was to determine whether there was any association between peripheral blood NKT-like cells and IVF treatment outcome. In this prospective study, 124 women who underwent IVF treatment for tubal factor were randomly selected in June and July 2011. Blood samples were obtained on the day of vaginal oocyte retrieval prior to the procedure. The percentages of peripheral blood NKT-like cell subsets and the expression levels of mRNA encoding MCP-1 and TNFα in PBMCs were recorded, and their relation to IVF treatment outcomes was analyzed. CD3+CD56+CD16+ NKT-like cells were significantly elevated in the pregnant group. The expression level of MCP-1 and TNFα mRNAs in PBMCs from the pregnant group was also increased. Furthermore, both MCP-1 and TNFα mRNA expression were positively correlated with the percentage of CD3+CD56+CD16+ NKT-like cells (r=0.55 and r=0.70, respectively). A ROC analysis (AUC=0.634) found that in those women with CD3+CD56+CD16+ NKT-like cells >1.85%, the pregnancy rate and live birth rate were higher than in women with cells below this level. An increase in CD3+CD56+CD16+ NKT-like cells was associated with a better IVF treatment outcome (OR 4.89, 95% CI=1.86-12.88), with a sensitivity of 47%, specificity of 85%, PPV of 89%, and NPV of 56%. We conclude that an elevated level of circulating CD3+CD56+CD16+ NKT-like cells is associated with increased rates of pregnancy and live births in IVF treatment.Journal of Reproductive Immunology 02/2013; DOI:10.1016/j.jri.2012.12.006 · 2.37 Impact Factor
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ABSTRACT: Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.Cellular & Molecular Immunology advance online publication, 11 August 2014; doi:10.1038/cmi.2014.68.Cellular & molecular immunology 08/2014; DOI:10.1038/cmi.2014.68 · 4.19 Impact Factor