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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Available from: Frans Claas, Jul 29, 2015
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    • "Among these adaptive T cells, regulatory forkhead box p3 (Foxp3) þ CD4 þ T cells, which are enriched in the decidua, have drawn much attention (Ernerudh, Berg, and Mjosberg 2011). Regarding the specificity of Treg cells there is growing evidence, in particular derived from mouse models, that they are induced by paternal antigens (reviewed in Guerin, Prins, and Robertson 2009; Leber, Teles, and Zenclussen 2010), with some supportive evidence from studies in humans regarding recognition of paternal antigens (Mjosberg et al. 2007) and enrichment of fetus-specific cells in decidua (Tilburgs et al. 2008). Interestingly, Treg cell induction is enhanced by exposure to semen, thus creating a specific immune tolerance that contributes to a successful subsequent pregnancy. "
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    • "There are contradictory data regarding the participation of antigen-dependent and independent mechanisms for Treg expansion during pregnancy [5] [6] [7]. Aluvihare and colleagues [8] showed that the increase in the number of CD4 + CD25 + T cells in syngeneically mated female mice is comparable to that of allogeneically mated females. "
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