CD4(+)CD25(+)FoxP3(+) regulatory T cells and cytokines interact with estradiol in cases of missed abortion

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.