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


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
    • ") and decreasing Treg cells in peripheral blood and the decidua of preeclampsia were reported (Sasaki et al., 2007; Santner-Nanan et al., 2009; Quinn et al., 2011; Toldi et al., 2012; Hsu et al., 2012). "
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    ABSTRACT: In oocyte donation (OD) pregnancies, a fetus is a complete allograft to the maternal host and OD pregnancies are an independent risk factor for preeclampsia. Immunocompetent cells contribute to spiral artery remodeling and the failure of this process could contribute to the pathophysiology of preeclampsia. Recent data have shown that impaired autophagy of extravillous trophoblasts (EVT) may induce poor vascular remodeling in preeclampsia. We have studied the distribution of T cells, NK cells and macrophages in the decidua basalis of 14 normotensive OD pregnancies, 5 preeclamptic OD cases, 16 normotensive pregnancy cases, and 13 preeclamptic cases in natural pregnancy or autologous oocyte IVF-ET (NP/IVF). The populations of decidual CD3(+)T cells, CD8(+)T cells, CD4(+)T cells, Foxp3(+)Treg cells, CD56(+)NK cells, and CD68(+) macrophages in preeclampsia were significantly smaller than those in normal pregnancy in NP/IVF. Those frequencies in normotensive OD pregnancies or preeclamptic cases in OD pregnancies were similar to those in preeclamptic cases in NP/IVF. Impaired vascular remodeling was observed in OD pregnancies, regardless of the presence or absence of preeclampsia. The expression of p62, an impaired autophagy marker in EVT of normotensive or preeclamptic OD pregnancies, was significantly higher than that in normal pregnancies in NP/IVF. Immunological change in the decidua basalis and impairment of autophagy in EVT may induce impairment of spiral artery remodeling in OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Journal of Reproductive Immunology 08/2015; DOI:10.1016/j.jri.2015.07.005 · 2.82 Impact Factor
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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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