Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Gasoowon-dong, Seo-gu, Daejeon 302-718, Korea.
Hum Reprod. 2011 Nov;26(11):2964-71. doi: 10.1093/humrep/der301. Epub 2011 Sep 15.
T cells which produce interleukin (IL)-17 are involved in chronic inflammatory processes and regulatory T (Treg) cells are possibly the most important immune regulators. We aimed to investigate peripheral blood IL-17(+) T and Foxp3(+) Treg cells in women with idiopathic recurrent pregnancy loss (RPL).
The study design is a cross-sectional evaluation of Th1, Th2, IL-17(+) T and Treg cells in women with idiopathic RPL (n = 42) and age-matched parous controls (n = 24). Flow cytometric analysis was performed to measure IL-17(+) T and Foxp3(+) Treg cells, and ratios of Th1/Th2 cells using anti-IL-17A and anti-Foxp3 antibodies, and monoclonal antibodies to tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-10. Student's t-test and partial correlations were applied for statistical analysis.
TNF-α-/IL-10-producing CD3(+)CD4(+) T cell ratio was higher in women with RPL than controls (P = 0.048). Levels of IL-17(+) T cells (P = 0.021) and the IL-17(+) T/CD4(+)Foxp3(+) Treg cell ratio (P = 0.001) were increased, whereas Foxp3(+) (P = 0.035), Foxp3(low) (P = 0.032) and CD4(+)Foxp3(+) T cell (P = 0.037) levels were decreased in women with RPL, compared with controls. Levels of IL-17(+) T cells were correlated with TNF-α-producing CD3(+)CD4(+) T cells (r = 0.269, P = 0.033), and with ratios of TNF-α/IL-10 (r = 0.276, P = 0.027) and IFN-γ/IL-10 (r = 0.266, P = 0.035)-producing CD3(+)CD4(+) cells. Furthermore, the ratio of IL-17(+) T cells to CD4(+)Foxp3(+) Treg cells showed a positive correlation with TNF-α-producing CD3(+)CD4(+) T cells (P = 0.047) and IFN-γ-producing CD3(+)CD4(+) T cells (P = 0.048) as well as a ratio of IFN-γ/IL-10-producing CD3(+)CD4(+) T cells (P = 0.037).
Enhanced pro-inflammatory immune responses with suppressed immune regulation may be an important immune mechanism involved in RPL.
产生白细胞介素 (IL)-17 的 T 细胞参与慢性炎症过程，调节性 T (Treg) 细胞可能是最重要的免疫调节剂。我们旨在研究特发性复发性妊娠丢失 (RPL) 妇女外周血中 IL-17(+)T 和 Foxp3(+)Treg 细胞。
本研究设计为特发性 RPL（n = 42）和年龄匹配的多产妇对照组（n = 24）的 Th1、Th2、IL-17(+)T 和 Treg 细胞的横断面评估。采用抗 IL-17A 和抗 Foxp3 抗体以及单克隆抗 TNF-α、IFN-γ 和 IL-10 抗体通过流式细胞术分析来测量 IL-17(+)T 和 Foxp3(+)Treg 细胞，以及 Th1/Th2 细胞的比值。应用学生 t 检验和偏相关进行统计分析。
与对照组相比，RPL 妇女 TNF-α/IL-10 产生的 CD3(+)CD4(+)T 细胞比值更高（P = 0.048）。IL-17(+)T 细胞水平（P = 0.021）和 IL-17(+)T/CD4(+)Foxp3(+)Treg 细胞比值（P = 0.001）升高，而 Foxp3(+)（P = 0.035）、Foxp3(low)（P = 0.032）和 CD4(+)Foxp3(+)T 细胞（P = 0.037）水平在 RPL 妇女中降低，与对照组相比。IL-17(+)T 细胞水平与 TNF-α 产生的 CD3(+)CD4(+)T 细胞相关（r = 0.269，P = 0.033），与 TNF-α/IL-10（r = 0.276，P = 0.027）和 IFN-γ/IL-10（r = 0.266，P = 0.035）产生的 CD3(+)CD4(+)细胞比值相关。此外，IL-17(+)T 细胞与 CD4(+)Foxp3(+)Treg 细胞的比值与 TNF-α 产生的 CD3(+)CD4(+)T 细胞（P = 0.047）和 IFN-γ 产生的 CD3(+)CD4(+)T 细胞（P = 0.048）以及 IFN-γ/IL-10 产生的 CD3(+)CD4(+)T 细胞比值呈正相关（P = 0.037）。
增强的促炎免疫反应伴随着抑制性免疫调节可能是 RPL 中涉及的重要免疫机制。
