Decidual CD4+CD25+CD127dim/- regulatory T cells in patients with unexplained recurrent spontaneous miscarriage.
ABSTRACT To investigate the frequency and function of CD4(+)CD25(+)CD127(dim/-) regulatory T (Treg) cells in decidua of patients with unexplained recurrent spontaneous miscarriage (URSM).
The decidual lymphocytes from patients who experienced URSM and normal pregnant women (controls) were collected by Ficoll density gradient centrifugation. CD4(+)CD25(+)CD127(dim/-) Treg cells were isolated by magnetic cell sorting. The proportion of Treg cells and IL-10, TGF-β in Treg cells were determined by flow cytometry. Inhibitory effects of Treg cells on effecter T cells were detected with or without the presentation of anti-IL-10 antibodies and anti-TGF-β antibodies.
The frequency of CD4(+)CD25(+)CD127(dim/-) Treg cells was decreased in URSM decidua compared to controls (2.09%±0.86% vs. 2.97%±1.19%, p=0.005), and the expression of IL-10 and TGF-β in Treg cells was lower in the URSM group than in the control group (p=0.04 and p=0.01, respectively). Furthermore, the suppressive effect of CD4(+)CD25(+)CD127(dim/-) Treg cells on the proliferation of effector T cells was decreased in URSM decidua (p<0.05). Suppression was mediated predominantly through IL-10 and TGF-β in decidua.
Decreased frequency and immunosuppressive capacity of CD4(+)CD25(+)CD127(dim/-) Treg cells was found in URSM decidua. Treg cells inhibit proliferation of effector T cells mainly via IL-10 and TGF-β in URSM decidua.
- SourceAvailable from: Ana C Zenclussen[Show abstract] [Hide abstract]
ABSTRACT: Regulatory T cells (Treg) are one of the most and best studied immune cell population during human and murine pregnancy, and there is a general consent about their expansion during pregnancy. However, the identification of new and more reliable Treg markers during the last years resulted in some controversies about the kinetics of various Treg subsets at different pregnancy stages. No doubt exists regarding the importance of Treg for a normal pregnancy as pregnancy complications like spontaneous abortion and preeclampsia could be associated with a reduced Treg number and activity. In future, more attention should be paid to bring established data from the bench to the bedside to force the development of adequate therapies for treatment of pregnancy complications. In this article, we summarize previous and recent data on several aspects of Treg biology during human and murine pregnancy.American Journal Of Reproductive Immunology 01/2013; · 3.32 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: B lymphocytes are pleiotropic cells belonging to the adaptive arm of the immune system. Although B cells were classically regarded for their capacity to produce antibodies, in the recent years, several other functions were attributed to these cells. B cells can uptake, process and present antigens as well as produce several cytokines that further influence immunity.Mammalian pregnancies represent a fascinating phenomenon in which the maternal immune system must be able to 'tolerate' the semi-allogenic fetus while simultaneously protecting the mother and the fetus against external pathogens. This requires a finely regulated balance between immune activation and tolerance. In this regard, B cells and the antibodies they produced were shown to actively participate in both, pregnancy well-being as well as pregnancy-associated pathologies.We discuss here the currently available information concerning the role of B cells in the context of pregnancy.American Journal Of Reproductive Immunology 01/2013; · 3.32 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to examine the interaction of estradiol (E2) with CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells and cytokines in cases of missed abortion (MA). The peripheral blood lymphocytes from patients with MA and controls (normal pregnancy and non-pregnant females) were isolated from the blood by Ficoll density gradient centrifugation. CD4(+)CD25(+) Treg cells were isolated from peripheral blood mononuclear cells (PBMCs). The frequencies of CD4(+)CD25(+)FoxP3(+) Treg cells and mRNA expression of transcription factor forkhead box protein 3 (FoxP3) in the peripheral blood of MA (n=33), normal pregnancy (n=33) and non-pregnant females (n=27) were determined by intracellular three-color flow cytometry and quantitative polymerase chain reaction (qPCR), respectively. The serum levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were measured by enzyme-linked immunosorbent assay (ELISA) and a chemiluminescent immunoassay was used to examine the serum E2 levels. It was observed that the percentage of Foxp3(+) T cells in the peripheral blood of patients with MA were lower compared with those in the normal pregnancy and healthy non-pregnant controls. The results demonstrated that MA patients exhibited decreased levels of a peripheral Th2-related cytokine (IL-4) and E2. Furthermore, the low levels of CD4(+)CD25(+)Foxp3(+) T cells and IL-4 correlated positively with serum concentrations of E2. The data indicated that maternal immunological changes may reverse maternal tolerance in MA, and this phenomenon may be due to the interaction of E2 with CD4(+)CD25(+)Foxp3(+) T cells and cytokines in MA.Experimental and therapeutic medicine 02/2014; 7(2):417-422. · 0.34 Impact Factor