淋巴细胞主动免疫治疗对不明原因复发流产患者Treg／Th17平衡的影响

Impact of lymphocyte immunization therapy on Treg/Th17 paradigm in patients with unexplained recurrent spontaneous abortion

目的探讨淋巴细胞主动免疫治疗（LIT）对不明原因复发流产（URSA）患者的Treg／Th17免疫平衡的影响。方法应用流式细胞学技术及ELISA法测量URSA患者LIT治疗前、后外周血Treg、Th17细胞所占淋巴细胞比例和血清IL-10、IL-17、TGF-β1水平，并对比及分析关联性。结果40例URSA患者LIT治疗后外周血CD4^＋CD25^＋Treg、CD4^＋CD25^＋CD127^lowTreg细胞所占比例高于治疗前，CD8^＋CD3^＋IL-17A^＋TH17细胞所占比例低于治疗前，且与前两者的改变分别呈负相关（r=-0．724，P〈0．01；r=-0．571，P〈0．01），Treg／Th17比例高于治疗前，差异有统计学意义。LIT治疗后血清IL-10、TGF-β1水平较治疗前升高，且分别与CD4^＋CD25^＋Treg细胞比例的改变呈正相关（r=0．654，P〈0．01；r=0．658，P〈0．01），IL-17水平降低，且与CD8^＋CD3^＋IL-17A^＋Th17细胞比例的改变呈正相关（r=0．693，P〈0．01），差异有统计学意义。结论LIT可能影响URSA患者的Treg／Th17免疫平衡，提高Treg细胞亚群的数量、功能，降低Th17细胞亚群的数量、功能，以此发挥治疗作用。

Objective To investigate the impact of lymphocyte immunization therapy （LIT） on Treg/Th17 paradigm in patients with unexplained recurrent spontaneous abortion （URSA）. Methods The proportion of Tregs and Thl7 cells in peripheral blood lymphocytes were measured by flow cytometry, and the concentration of IL-10, TGF-β1, and IL-17 in serum were measured by ELISA. Results In 40 URSA patients, the proportions of CD4^＋ CD25^＋ Treg and CD4^＋ CD25^＋ CD127^lowTreg cells in peripheral blood were significantly increased after LIT treatment （both P 〈 0.05 ）. The proportion of CD8^＋CD3^＋ IL-17A^＋ Th17 cell was significantly reduced after treatment （P 〈0.05）, and the number of this cell was negatively correlated with the former two （ r = - 0.724, P 〈 0.01 ; r = - 0.571, P 〈 0.01 ）. The concentrations of IL-10 and TGF-β1 in serum were both significantly increased after LIT treatment （both P〈0.05）, and the increments of IL-10 and TGF-β1 were positively correlated to the change of CD4^＋ CD25^＋ Treg ratio （ r = 0.654, P 〈 0.01 ; r = 0. 658, P 〈0.01, respectively）. The concentration of IL-17 in serum was markedly decreased after LIT treatment （ P 〈 0.05 ）, and its decrement showed a positive correlation with the change of CD8^＋ CD3^＋ IL-17A^＋ Th17 cell ratio （r = 0. 693, P〈0.01）. Conclusion LIT may work through affecting the Treg/Th17 paradigm and increasing the function and amount of Treg cells while reducing Th17 cells.