Department of Obstetrics and Perinatology, Medical University of Lublin, Poland.
J Reprod Immunol. 2012 Mar;93(2):75-81. doi: 10.1016/j.jri.2012.01.006. Epub 2012 Feb 25.
The aim of this study was to estimate the prevalence of CD3(+)CD4(+) T lymphocytes producing IL-17, IL-2, IFN-γ, and IL-4, plus CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells, in peripheral blood of patients with preeclampsia and healthy women in the third trimester of normal pregnancy. Another purpose was to assess the immunosuppressive activity of Treg cells from patients with preeclampsia compared with controls. Thirty-four preeclampsia patients and 27 healthy pregnant women were included. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells and CD3(+)CD4(+) T lymphocytes with intracellular expressions of cytokines were estimated using monoclonal antibodies and flow cytometry. In vitro functional assays were performed using a Treg Cell Isolation Kit and (3)H-thymidine incorporation assays. The percentage of CD3(+)CD4(+) T lymphocytes producing IL-17A was significantly higher in preeclampsia than in healthy, normotensive pregnant women in the third trimester (p<0.001). The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in the study group compared with controls (p<0.05). There was no change in the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes from preeclampsia patients without Treg cells and after addition of autologous Treg cells. In normal pregnancy, the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes was significantly higher without Treg cells compared with the response after addition of autologous Treg cells (p<0.05). The results suggest up-regulation of the Th17 immune response in preeclampsia. The decreased number and function of Treg cells may be responsible for activating the inflammatory response characteristic of this disorder. In preeclampsia, the predominance of Th17 immunity could act through modulating the Th1/Th2 immune balance.
本研究旨在评估子痫前期患者和正常妊娠晚期健康妇女外周血中 CD3(+)CD4(+)T 淋巴细胞产生白介素-17（IL-17）、白介素-2（IL-2）、干扰素-γ（IFN-γ）和白介素-4（IL-4）的比例，以及 CD4(+)CD25(+)FoxP3(+)T 调节（Treg）细胞的数量。另一目的是评估与对照组相比，子痫前期患者 Treg 细胞的免疫抑制活性。共纳入 34 例子痫前期患者和 27 例正常妊娠晚期健康妇女。采用单克隆抗体和流式细胞术检测 CD4(+)CD25(+)FoxP3(+)Treg 细胞和细胞内细胞因子表达的 CD3(+)CD4(+)T 淋巴细胞的百分比。采用 Treg 细胞分离试剂盒和（3）H-胸腺嘧啶掺入法进行体外功能测定。子痫前期患者外周血中 CD3(+)CD4(+)T 淋巴细胞产生白介素-17A 的比例明显高于正常妊娠晚期健康妇女（p<0.001）。与对照组相比，研究组 CD4(+)CD25(+)FoxP3(+)Treg 细胞的比例显著降低（p<0.05）。无 Treg 细胞的子痫前期患者和加入自体 Treg 细胞后，CD3(+)CD4(+)CD25(-)T 淋巴细胞的刺激指数没有变化。在正常妊娠中，无 Treg 细胞的 CD3(+)CD4(+)CD25(-)T 淋巴细胞刺激指数明显高于加入自体 Treg 细胞后的反应（p<0.05）。结果表明，子痫前期患者 Th17 免疫反应上调。Treg 细胞数量和功能的减少可能是导致这种疾病特征性炎症反应激活的原因。在子痫前期中，Th17 免疫的优势可能通过调节 Th1/Th2 免疫平衡来发挥作用。
