The Costimulatory Signal Upregulation is Associated with Th1 Bias at the Maternal-Fetal Interface in Human Miscarriage
The Costimulatory Signal Upregulation is Associated with Th1 Bias at the Maternal-Fetal Interface in Human Miscarriage
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DOI：
10.1111/j.1600-0897.2011.00997.x
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
Li, Da-Jin
中科院分区：
文献类型：
--
作者：
Jin, Li-Ping;Fan, Deng-Xuan;Li, Da-Jin
目的：探讨在人类妊娠丢失中，共刺激信号调节是否与母胎界面上辅助性T细胞1/辅助性T细胞2 （Th1/Th2）偏倚有关。研究方法采用qPCR和Western blot方法比较正常早孕和流产小鼠蜕膜组织中CD80、CD86及蜕膜T细胞中CD28和细胞毒性T淋巴细胞抗原-4 （CTLA-4）的表达。流式细胞术检测蜕膜T细胞细胞因子的产生。分析共刺激分子表达与Th1/Th2细胞因子的相关性。结果CD80 mRNA和蛋白表达在正常妊娠和流产组无显著差异。与妊娠早期相比，流产时CD28和CD86表达升高，CTLA-4表达降低。流产时个体T细胞中白细胞介素(IL)-2和干扰素-c （ifn - γ）表达升高，IL-4和IL-10表达降低。相关分析显示，CD86和CD28的表达与Th1细胞因子（IL-2和ifn - γ）的产生呈显著正相关，CTLA-4的表达与Th1细胞因子的产生呈显著负相关。结论T细胞共刺激信号的上调可能在母胎界面形成异常的免疫微环境，向Th1反应转变，从而导致人类流产。
ProblemTo evaluate whether the association of the costimulatory signal regulation with T helper 1/T helper 2 (Th1/Th2) bias at maternal-fetal interface in human pregnancy loss.Method of studyThe expression of CD80 and CD86 in decidual tissues and CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in the decidual T cells was compared between normal early pregnancy and miscarriage by qPCR and Western blot. The cytokine production in decidual T cells was performed by flow cytometry. The correlation of costimulatory molecule expression with Th1/Th2 cytokines was analyzed.ResultsThe CD80 mRNA and protein expression showed no significant difference between normal pregnancy and miscarriage. An increase in the expression of CD28 and CD86 was accompanied by a decrease in the expression of CTLA-4 in miscarriage in comparison with the early pregnancy. The higher expression of interleukin (IL)-2 and interferon-c (IFN-gamma), and lower expression of IL-4 and IL-10 in the decidual T cells were present in miscarriage. A correlation analysis showed a significant positive correlation of CD86 and CD28 expression with the Th1 cytokine production (IL-2 and IFN-gamma), a significant negative correlation of CTLA-4 expression with the Th1 cytokine production.ConclusionThe upregualtion of costimulatory signals on T cells might form an abnormal immune microenvironment, a shift to Th1 responses, at maternal-fetal interface, which leads to human miscarriage.