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Evidence for a Selective Migration of Fetus-Specific CD4 + CD25bright Regulatory T Cells from the Peripheral Blood to the Decidua in Human Pregnancy

Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
The Journal of Immunology (Impact Factor: 5.36). 05/2008; 180(8):5737-45. DOI: 10.4049/jimmunol.180.8.5737
Source: PubMed

ABSTRACT During pregnancy, the maternal immune system has to tolerate the persistence of fetal alloantigens. Many mechanisms contribute to the prevention of a destructive immune response mediated by maternal alloreactive lymphocytes directed against the allogeneic fetus. Murine studies suggest that CD4(+)CD25(+) T cells provide mechanisms of specific immune tolerance to fetal alloantigens during pregnancy. Previous studies by our group demonstrate that a significantly higher percentage of activated T cells and CD4(+)CD25(bright) T cells are present in decidual tissue in comparison with maternal peripheral blood in human pregnancy. In this study, we examined the phenotypic and functional properties of CD4(+)CD25(bright) T cells derived from maternal peripheral blood and decidual tissue. Depletion of CD4(+)CD25(bright) T cells from maternal peripheral blood demonstrates regulation to third party umbilical cord blood cells comparable to nonpregnant controls, whereas the suppressive capacity to umbilical cord blood cells of her own child is absent. Furthermore, maternal peripheral blood shows a reduced percentage of CD4(+)CD25(bright)FOXP3(+) and CD4(+)CD25(bright)HLA-DR(+) cells compared with peripheral blood of nonpregnant controls. In contrast, decidual lymphocyte isolates contain high percentages of CD4(+)CD25(bright) T cells with a regulatory phenotype that is able to down-regulate fetus-specific and fetus-nonspecific immune responses. These data suggest a preferential recruitment of fetus-specific regulatory T cells from maternal peripheral blood to the fetal-maternal interface, where they may contribute to the local regulation of fetus-specific responses.

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    • "They showed afterwards that the transferred Treg cells act by creating a privileged tolerant environment, and by up-regulating leukemia inhibitory factor (LIF), TGF-β, and HO-1 levels (25). Tilburgs et al. reported selective migration of specific Treg cells from blood to the decidua in human pregnancy (26). Then, seminal fluid was shown to drive expansion of CD4+CD25+ cells in mouse (27). "
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    Frontiers in Endocrinology 07/2014; 5:106. DOI:10.3389/fendo.2014.00106
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    • "Given the decidua is the fetal–maternal interface and the likely place of fetal antigen encounter, it is not surprising that the proportion of Treg cells is even greater in the decidua during pregnancy compared to the peripheral blood (77, 78). The question is whether these Treg cells are recruited from the peripheral blood or induced locally. "
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    ABSTRACT: Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface - the decidua, the site of implantation, and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, pre-eclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages) make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3(+) regulatory T cells are crucial for ensuring immune tolerance toward the semi-allogeneic fetus. Additionally, another population of CD4(+)HLA-G(+) suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy.
    Frontiers in Immunology 03/2014; 5:125. DOI:10.3389/fimmu.2014.00125
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    • "The highly protective environment and need to avoid immunological interactions of the fetus against the mother seem to be the main reason for this “physiological” immaturity of the immune system in newborn infants. Regulatory T cells (Tregs) are particularly abundant and potent during pregnancy and at birth and inhibit excessive immune responses whereby ultimately the maintenance of peripheral T-cell tolerance and pathogen clearance are key [1,2,3,4]. Moreover the signaling within the intestine through pathogen recognition receptors like the toll like receptor (TLR) family for instance is crucial for the generation of effective immunity. Illustrative for this is that TLR2 influences the function of Tregs [5] and establishes a direct link between the intestinal microbiota and the control of immune responses through Tregs [6]. "
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