Analysis of the frequencies and functions of CD4+CD25+CD127low/neg, CD4+HLA-G+, and CD8+HLA-G+ regulatory T cells in pre-eclampsia

Abstract

Most of the investigations on regulatory T cells (Treg) have focused on CD4+CD25+Foxp3+ Treg cells. Although new subsets of these cells such as CD4+CD25+CD127low/neg, CD4+HLA-G+, and CD8+HLA-G+ Treg cells have been introduced, documents regarding these populations are limited or controversial in case of pregnancy and pre-eclampsia (PE). Here, we investigated the frequencies of the three aforementioned Treg cell subsets in the peripheral blood of non-pregnant (n = 15), healthy pregnant, and preeclamptic women (n = 17 in each group) using flow cytometry. We also assessed the ability of the isolated CD4+CD25+CD127low/neg and CD4+HLA-G+ Treg cells to suppress responder T cells proliferation and cytokine secretion using CFSE dye dilution and ELISA technique. Our results showed that the frequency of CD4+CD25+CD127low/neg Treg cells was significantly lower in preeclamptic women (p = 0.001). Also, this subset negatively correlated with both systolic (R= - 0.401, p = 0.004) and diastolic (R= - 0.541, p = 0.001) blood pressures. Regarding CD4+HLA-G+ and CD8+HLA-G+ Treg cells, the mean percentages of these cells were significantly higher in the context of normal pregnancy (p < 0.01). Finally, our results in the functional assay experiments did not show statistically significant differences between groups (p ≥ 0.05), but they reveal a shift toward the lower suppressive capacity of CD4+CD25+CD127low/neg and CD4+HLA-G+ Treg cells in preeclamptic patients which might be clinically important. In conclusion, a significant decrease in the frequency of Treg cell subsets and also a shift toward the lower suppressive capacity of these cells in preeclamptic patients may lead to immunological maladaptation in the context of PE.