Proportion of peripheral blood and decidual CD4 CD25 regulatory T cells in pre-eclampsia

Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan.
Clinical & Experimental Immunology (Impact Factor: 3.04). 07/2007; 149(1):139-45. DOI: 10.1111/j.1365-2249.2007.03397.x
Source: PubMed

ABSTRACT CD4(+) CD25(bright) regulatory T (T(reg)) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4(+) CD25(bright) T(reg) cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3(+)) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25(bright) cells within the CD4(+) T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0.001) and non-pregnant healthy controls (P < 0.001). Also, the percentage of FoxP3(+) cells within CD3(+) T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of T(reg) cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.

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Available from: Arihiro Shiozaki, Feb 04, 2015
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    • "A great step toward the further elucidation of the networks involved in such a dialog was the discovery by Asif Ahmed and Guillermina Girardi that the CBA × DBA/2 murine abortion model was also a murine model of preeclampsia (Ahmed et al., 2010), and further studies led to the discovery of the pivotal role of complement activation (Girardi et al., 2006). Turning to the protective effects, the renaissance of T cells as Tregs was a pivotal event, and an integrated model of preparation of the uterus for implantation under the influence of sperm and seminal fluids in this respect is now emerging (Tremellen et al., 1998; Robertson et al., 2003; Sasaki et al., 2007). Treg lymphocytes appear to be ideal candidates, too, to explain the memory throughout successive pregnancies (beginning at the time of contact between the cervix and sperm) (Clark and Chaouat, 2012). "
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    ABSTRACT: This workshop had four main objectives: (A) Trying to look at the preeclampsia (PE) problem "from the Space Shuttle": why preeclampsia has emerged in humans (a specific human reproductive feature among 4300 mammal species)? (B) Epidemiology: there are major geographical differences concerning early onset PE and late onset PE throughout the world. (C) Vascular: The very promising use of pravastatin in the treatment of the vascular maternal syndrome (based on the metabolism of carbon monoxide (CO), the role of inositol phosphate glycans P-type (IPG-P), a major role in comprehending the insulin resistance phenotype in preeclampsia. (D) Immunology: the specialty of these workshops since their start in 1998; our understanding of the role of the immune system and the regulation of the deep implantation of the human trophoblast (and the obligatory compromises between the fetal/placental unit and the mother) have reached a kind of "maturity," following the pivotal studies exploring the biology of repetitive sperm exposure in the female genital tract. The meeting of people who never meet each other in the course of their normal professional lives (obstetricians, evolutionists, geneticists, immunologists, fundamentalist vascular biologists, epidemiologists, anthropologists, neonatologists, etc.) permitted some fruitful reflections to be made again this year. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Journal of Reproductive Immunology 07/2015; DOI:10.1016/j.jri.2015.07.001 · 2.82 Impact Factor
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    • "The suppressor activity of iTregs in those patients is also decreased (36). Regarding preeclampsia (PE), it has been reported that PE patients present decreased Treg cell level in blood and in decidua (17, 37, 38). Moreover, Treg cell function has been found to be decreased in PE patients (39). "
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    ABSTRACT: Acceptance of the fetal semi-allograft by the mother's immune system has become the focus of intensive research. CD4+ T cells are important actors in the establishment of pregnancy. Th1/Th2 paradigm has been expanded to include CD4+ regulatory T (Treg) and T helper 17 (Th17) cells. Pregnancy hormones exert very significant modulatory properties on the maternal immune system. In this review, we describe mechanisms by which the endocrine milieu modulates CD4 T cell polarization during pregnancy. We first focused on Treg and Th17 cells and on their importance for pregnancy. Secondly, we review the effects of pregnancy hormones [progesterone (P4) and estradiol (E2)] on immune cells previously described, with a particular attention to human chorionic gonadotropin (hCG). The importance of Treg cells for pregnancy is evidenced. They are recruited before implantation and are essential for pregnancy maintenance. Decreased number or less efficient Treg cells are implicated in fertility disorders. As for Th17 cells, the few available studies suggest that they have a negative impact on fertility. Th17 frequency is increased in infertile patients. With the combination of its pro-effects on Th2 and Treg cells and anti-effects on Th1 and Th17 cells, P4 contributes to establishment of a favorable environment for pregnancy. E2 effects are more dependent on the context but it seems that E2 promotes Treg and Th2 cells while it inhibits Th1 cells. hCG positively influences activities of Treg and uterine natural killer cells. This embryo signal is an essential actor for the success of pregnancy, both as the endocrine factor regulating P4 secretion by the ovarian corpus luteum, but also as a paracrine agent during implantation as well as an angiogenic and immunologic mediator during the course of gestation. Luteinizing hormone (LH) immune properties begin to be studied but its positive impact on Treg cells suggests that LH could be a considerable immunomodulator in the mouse.
    Frontiers in Endocrinology 07/2014; 5:106. DOI:10.3389/fendo.2014.00106
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    • "Combined positivity for any of the TLR-4 and NOD2 allelic variants and high levels of IL-6 were 6.9-fold more common in women with a history of early-onset preeclampsia than in healthy pregnant women (OR 6.9) (Table 2) [52]. In women with preeclampsia a persistent TLR-4 signal could reverse the CD4+CD25bright Treg cell-mediated immunosuppression [82]. This means that the TLR-4 pathway and the innate immune system might be involved in development of both the HELLP syndrome and early-onset preeclampsia [52]. "
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    ABSTRACT: Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the -670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.
    Journal of pregnancy 06/2014; 2014:910751. DOI:10.1155/2014/910751
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