肝内调节性T淋巴细胞与辅助陛T淋巴细胞17平衡在不同阶段慢性乙型肝炎病毒感染者中的作用  

The role of intrahepatic regulatory T cells/helper thymphorytes 17 balance in patients with different phases of chronic hepatitis B virus infection

作　　者：马海霞 李嘉[1] 刘勇钢[1] 武婷 高敏[1] 周莉[1] 陆伟[1,3] Ma Haixia;Li Jia;Liu Yonggang;Wu Ting;Gao Min;Zhou Li;Lu Wei(Tianjin Medical Institute of Hepatology , Tianjin Second People＇s Hospital, Tianjin 300192, China)

机构地区：[1]天津市第二人民医院 天津市肝病医学研究所,300192 [2]厦门大学附属第一医院感染科 [3]天津市第一中心医院消化科

出　　处：《中华传染病杂志》2018年第3期133-138,共6页Chinese Journal of Infectious Diseases

基　　金：天津市卫生行业重点攻关项目（13KG126）

摘　　要：目的 分析不同阶段慢性HBV感染者肝内Treg/Th17平衡变化,探讨Treg/Th17平衡在维持免疫耐受和介导免疫清除中的作用以及对病情进展的影响.方法 纳入天津市第二人民医院68例行肝活组织检查的慢性HBV感染者,免疫耐受期20例,清除期36例,非活动期12例.另设健康对照8名.免疫组织化学法检测肝内Treg和Th17.分析各组患者肝内Treg/Th17变化及清除期患者入院2周时外周血HBsAg、HBeAg和HBV DNA下降幅度与Treg/Th17之间关系.结果 Treg和Th17水平均为清除期组〉非活动期组〉耐受期组〉对照组,其中清除期组的Treg与其他3组间差异均有统计学意义（均P〈0.01）,其他各组间差异无统计学意义（均P〉0.05）;耐受期组Th17与对照组间差异无统计学意义（P〉0.05）,其他各组间差异也无统计系学意义（均P〈0.05）.Treg/Th17比值表现为耐受期组〉对照组〉非活动期组〉清除期组,其中清除期组与对照和耐受期组间以及非活动期和耐受期组间差异有统计学意义（均P〈0.05）,其他各组间差异均无统计学意义（均P〉0.05）.清除期患者入院2周时外周血HBsAg、HBeAg和HBVDNA下降幅度与肝内Treg水平呈显著负相关（r分别为-0.941、-0.869和-0.883,均P〈0.01）;炎症程度分级（G）和纤维化分期（S）不同的清除期患者肝内Treg、Th17水平及其比值均G4组〉G3组〉G2组、S3组〉S2组〉S1组,且差异有统计学意义（均P〈0.05）.结论 Treg/Th17在耐受期HBV感染者并未失衡,Treg在维持HBV免疫耐受中并未发挥作用;Treg/Th17在免疫清除期出现失衡,Th17促进炎性反应及纤维化形成,而Treg通过负反馈调节机制,抑制炎性反应和减少肝损伤的同时,也阻碍了HBV的清除.Objective To analyze the change of intrahepatic regulatory T cells （Treg ）/helper thymphorytes （Th）17 balance in patients with different phases of chronic hepatitis B virus （HBV ） infection ,and to explore the role of Treg/Th17 balance in maintaining immune tolerance and inducing immune clearance ,and its influence on disease progression .Methods Sixty-eight patients with chronic HBV infection who underwent liver biopsy in Tianjin Second People′s Hospital were included .The 68 patients included 20 cases in immune tolerant （IT） phase ,36 cases in immune clearance （IC） phase and 12 cases in inactive phase .Eight healthy liver transplant donors were collected as healthy controls .The intrahepatic Treg/Th17 levels were detected by immuno-histochemical method . The changes of Treg/Th17 balance in patients with different phases of chronic HBV infection ,and the relationship between Treg/Th17 balance and the decreases of hepatitis B surface antigen （HBsAg ） , hepatitis B antigen （HBeAg） and HBV DNA levels in the peripheral blood were analyzed in patients with IC phase at two weeks of admission .Results The intrahepatic Treg and Th17 levels in IC phase group were the highest , then and they were higher in inactive phase group were higher than those in IT phase group ,And they were the lowest in control group .The Treg level in IC phase group increased significantly compared with the other three groups （all P〈 0 .01） ,and there were no significant differences among the other three groups （all P〉 0 .05） .The Th17 level between IT phase group and inactive phase group was not significantly different （P〉 0 .05） ,while the differences were not significant in other groups （all P〉0 .05） .Treg/Th17 ratio of IT phase group was the highest ,then the ratio of control group was higher than that of inactive phase group ,and IC phase group was the lowest ratio .The differences between IC phase group ,control group and IT phase group were significant （all P〈 0 .05） ,and the dif

关 键 词：T淋巴细胞 调节性 慢性HBV感染 免疫耐受期 免疫清除期 THL7 

分 类 号：R512.62[医药卫生—内科学]