干预协同刺激信号诱导不明原因早期复发性流产患者外周血Th1/Th2转换的体外研究

目的观察体外干预细胞毒性T细胞相关抗原4(CTLA-4)对不明原因早期复发性流产(URSA)患者外周血辅助性T细胞(Th)1/Th2转换的影响。方法用人绒毛膜癌细胞株JEG-3制备的滋养细胞抗原刺激30例URSA患者外周血单核细胞,分为实验组A:加重组蛋白CTLA-4Ig(10和1 mg/L)组,实验组B:加CTLA-4抗体(10和1 mg/L)组;对照组:加IgG(10和1 mg/L)组。采用酶联免疫吸附试验(ELISIA)测上清液中白细胞介素(IL)-2、干扰素γ(IFN-γ)和IL-4水平。结果与相应浓度的对照组相比,CTLA-4Ig组IL-4水平显著升高(P<0.05),IL-2显著降低(P<0.05),IFN-γ两组间无显著性差异(P>0.05);而CTLA-4抗体组IL-4水平均显著低于对照组(P<0.01),而IFN-γ、IL-2水平均明显高于对照组(P<0.05)。CTLA-4Ig 10 mg/L组与CTLA-4Ig 1mg/L组比较,IL-4显著升高(P<0.05),IL-2显著降低(P<0.05),IFN-γ两组间无显著性差异(P>0.05)。与同浓度的对照组及CTLA-4抗体1 mg/L组相比,CTLA-4抗体10 mg/L组IL-4较低,而IFN-γ和IL-2稍高,但两组间亦无显著性差异(P>0.05)。结论CTLA-4Ig使URSA患者Th1/Th2型细胞因子向Th2型细胞因子偏移,有利于URSA的治疗;而CTLA-4抗体可以上调Th1型细胞因子,下调Th2型细胞因子,不利于妊娠。

Influence of the blockade of co-stimulation on Th1/Th2 shift in the patient with unexplained early recurrent spontaneous abortion in vitro

Objectives: To study the influence of blockade of co-stimulation on Th1/Th2 cytokine shift in the patients with unexplained early recurrent spontaneous abortion(URSA).Methods: Maternal peripheral blood mononuclear cells(PBMC) were collected from 30 UERSA patients and cultured.Cytokine synthesis was induced by antigens from a choriocarcinoma cell line of JEG-3(CTLA-4Ig or anti-CTLA4 antibody),with IgG as control.The levels of IL-2,IFN-γ and IL-4 were assessed by ELISA in the culture media.Results: We detected significantly higher levels of the Th2 cytokine IL-4(P<0.05),lower levels of the Th1 cytokine IL-2(P<0.05) and the same levels of IFN-γ(P>0.05) in CTLA-4Ig group,as compared with those in control group at the same concentration.The same results were found in CTLA-4Ig groups at different concentrations.We detected significantly higher levels of IL-2,IFN-γ(P<0.05) and lower levels of IL-4(P<0.01) in anti-CTLA4 antibody group in comparison with the control group at the same concentration.In CTLA-4Ig group,there was no significant difference between different concentrations(P>0.05). Conclusions: CTLA-4Ig could block the co-stimulation to switch T cells from Th1 to Th2 in URSA patients,which might be a promising treatment for URSA,while anti-CTLA4 antibody can up-regulate Th1-type cytokines and down-regulate Th2-type cytokines,and is unfavorable to pregnancy in URSA patients.