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分析子痫前期中 CD4CD25CD127+、CD4HLA-G+ 和 CD8HLA-G+ 调节性 T 细胞的频率和功能。

Analysis of the frequencies and functions of CD4CD25CD127, CD4HLA-G, and CD8HLA-G regulatory T cells in pre-eclampsia.

机构信息

Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Obstetrics and Gynecology, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

J Reprod Immunol. 2019 Jun;133:43-51. doi: 10.1016/j.jri.2019.06.002. Epub 2019 Jun 21.

Abstract

Most of the investigations on regulatory T cells (Treg) have focused on CD4CD25Foxp3 Treg cells. Although new subsets of these cells such as CD4CD25CD127, CD4HLA-G, and CD8HLA-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 CD4CD25CD127 and CD4HLA-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 CD4CD25CD127 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 CD4HLA-G and CD8HLA-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 CD4CD25CD127 and CD4HLA-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.

摘要

大多数关于调节性 T 细胞(Treg)的研究都集中在 CD4CD25Foxp3 Treg 细胞上。尽管已经引入了这些细胞的新亚群,如 CD4CD25CD127、CD4HLA-G 和 CD8HLA-G Treg 细胞,但关于这些群体的文献在妊娠和子痫前期(PE)的情况下是有限的或有争议的。在这里,我们使用流式细胞术研究了外周血中非妊娠(n=15)、健康妊娠和子痫前期妇女(每组 n=17)中上述三种 Treg 细胞亚群的频率。我们还评估了分离的 CD4CD25CD127 和 CD4HLA-G Treg 细胞抑制应答 T 细胞增殖和细胞因子分泌的能力,使用 CFSE 染料稀释和 ELISA 技术。我们的结果表明,子痫前期妇女中 CD4CD25CD127 Treg 细胞的频率显著降低(p=0.001)。此外,该亚群与收缩压(R=-0.401,p=0.004)和舒张压(R=-0.541,p=0.001)均呈负相关。关于 CD4HLA-G 和 CD8HLA-G Treg 细胞,在正常妊娠情况下,这些细胞的平均百分比显著升高(p<0.01)。最后,我们在功能测定实验中的结果显示各组之间没有统计学上的显著差异(p≥0.05),但它们揭示了子痫前期患者中 CD4CD25CD127 和 CD4HLA-G Treg 细胞的抑制能力向较低水平的偏移,这可能具有临床意义。总之,子痫前期患者 Treg 细胞亚群的频率显著降低,以及这些细胞的抑制能力向较低水平偏移,可能导致 PE 中免疫失调。

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