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Title: Analysis of the frequencies and functions of CD4⁺CD25⁺CD127^low/neg, CD4⁺HLA-G⁺, and CD8⁺HLA-G⁺ regulatory T cells in pre-eclampsia.
Author: Zare M, Namavar Jahromi B, Gharesi-Fard B.
Journal: J Reprod Immunol; 2019 Jun; 133():43-51. PubMed ID: 31255887.
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⁺CD127^low/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⁺CD127^low/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⁺CD127^low/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⁺CD127^low/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.

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