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
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    • ") 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.
    Full-text · Article · Aug 2015 · Journal of Reproductive Immunology
    • "There are few defi nitive studies in humans focussed on evaluating effects of seminal fl uid, but clinical studies point to a consistent benefi cial effect in improving the chance of conception and protecting from immune-mediated gestational disorders such as preeclampsia. Preeclampsia is characterised by a signifi cant reduction in peripheral blood CD4 + CD25 high T regulatory cells and decidual Foxp3-positive cells within the CD3 + population (Sasaki et al. 2007 ). The altered Treg cell numbers may in part be due to altered seminal fl uid function, with extensive evidence pointing to an important role for TGFB in regulating human Treg cell reactivity and autoimmunity (Rubtsov and Rudensky 2007 ). "
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    ABSTRACT: Carriage of sperm is not the only function of seminal fluid in mammals. Studies in mice show that at conception, seminal fluid interacts with the female reproductive tract to induce responses which influence whether or not pregnancy will occur, and to set in train effects that help shape subsequent fetal development. In particular, seminal fluid initiates female immune adaptation processes required to tolerate male transplantation antigens present in seminal fluid and inherited by the conceptus. A tolerogenic immune environment to facilitate pregnancy depends on regulatory T cells (Treg cells), which recognise male antigens and function to suppress inflammation and immune rejection responses. The female response to seminal fluid stimulates the generation of Treg cells that protect the conceptus from inflammatory damage, to support implantation and placental development. Seminal fluid also elicits molecular and cellular changes in the oviduct and endometrium that directly promote embryo development and implantation competence. The plasma fraction of seminal fluid plays a key role in this process with soluble factors, including TGFB, prostaglandin-E, and TLR4 ligands, demonstrated to contribute to the peri-conception immune environment. Recent studies show that conception in the absence of seminal plasma in mice impairs embryo development and alters fetal development to impact the phenotype of offspring, with adverse effects on adult metabolic function particularly in males. This review summarises our current understanding of the molecular responses to seminal fluid and how this contributes to the establishment of pregnancy, generation of an immune-regulatory environment and programming long-term offspring health.
    No preview · Article · Jul 2015 · Advances in Experimental Medicine and Biology
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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.
    Full-text · Article · Jul 2015 · Journal of Reproductive Immunology
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