辅助性T淋巴细胞及其效应分子在慢性乙型肝炎患者疾病加重过程中的变化和作用  

Changes and effects of helper T cells and their effector molecules on disease aggravation in patients with chronic hepatitis B

作　　者：莫瑞东[1] 项晓刚[1] 王芃[1] 赖荣陶[1] 赵钢德[1] 刘昱含[1] 周慧娟[1] 郭斯敏[1] 韩艳[1] 蔡伟[1] 王晖[1] 谢青[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025

出　　处：《中华传染病杂志》2014年第4期209-213,共5页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金资助项目（81171569）;上海市科委优秀学术带头人项目（12XD1403600）;国家十二五科技重大专项（2012ZX10002007-002-004,2012ZX10002004-003）

摘　　要：目的 探讨Th1 、Th17和Th22及其效应分子γ干扰素、IL-17和IL-22在CHB活动期及慢加急性肝衰竭（ACLF）中的作用.方法 上海交通大学医学院附属瑞金医院感染科住院的CHB患者45例,ACLF患者38例,同时收集健康志愿者（HC）26名.采集患者及健康志愿者新鲜全血,体外刺激培养后细胞表面及胞内染色,行流式细胞分析;同时收集受试者血浆,ELISA检测血浆IL-22等细胞因子表达.两组比较采用非配对t检验,相关性分析采用Spearman检验.结果 CHB组和ACLF组患者Th1频数分别为18.17％±9.01％和15.49％±9.06％,较健康对照组的22.45％±7.90％明显降低（t值分别为2.017和3.175,P值分别为0.048和0.002）.ACLF组Th17频数为2.96％±1.30％,健康对照组为2.04％±0.91％,两组比较差异有统计学意义（t=3.121,P=0.003）;同时ACLF组与CHB组比较差异亦有统计学意义（t=2.875,P=0.005）.CHB组和ACLF组患者Th22频数较健康对照组明显升高（t值分别为2.128和3.995,P值分别为0.037和0.000）.CHB组患者血浆γ干扰素水平为（25.65±10.18） pg/mL,IL-22水平为（24.06±13.11） pg/mL,明显高于健康对照组的（12.95±6.63） pg/mL和（15.08±8.51） pg/mL（t值分别为5.390和2.961,P值分别为0.000和0.004）.ACLF组患者血浆IL-17和IL-22水平与健康对照组比较差异均有统计学意义（t值分别为2.654和4.123,P值分别为0.011和0.000）.IL-22水平与外周血中Th22频数呈正相关（r=0.549,P=0.012）.CHB组Th1频数与A LT、AST呈负相关（r值分别为-0.300和-0.384,P值分别为0.045和0.009）.ACLF组患者Th22频数与终末期肝病模型评分呈正相关（r=0.345,P=0.034）.结论 Th22和IL-22可能在CHB活动期和ACLF中起重要作用,深入研究Th22和IL-22在CHB和ACLF中的作用机制及其与疾病预后转归的关系,具有重要意义.Objective To investigate the role of helper T cell （Th）1,Th17 and Th22 and their effector molecules including interferon-gamma,interleukin （IL）-17 and IL-22 in active phase of chronic hepatitis B （CHB） and acute-on-chronic liver failure （ACLF）.Methods Forty-five CHB patients and 38 ACLF patients at Ruijin Hospital of Shanghai Jiaotong University School of Medicine were included,and 26 healthy controls （HC） were also enrolled.Fresh heparinized peripheral blood was obtained and stimulated in vitro with the phorbol myristate acetate and ionomycin.Surface and intracellular staining were performed,then detected by flow cytometry.Plasma was also collected from all subjects for the detection of cytokine concentration such as IL-22 by enzyme-linked immunosorbent assay.Difference between two groups was analyzed by unpaired t test.Spearman correlation test was used for correlation analysis.Results The Th1 frequencies in CHB and ACLF groups were 18.17 % ±9.01 % and 15.49 % ± 9.06%,respectively,which were both significantly decreased compared with HC group （22.45% ± 7.90%; t=2.017,P=0.048 andt=3.175,P=0.002,respectively）.The frequency of Th17 in ACLF patients （2.96%±1.30%） was significantly increased compared with HC （2.04%±0.91%）（t=3.121,P=0.003） and CHB group （t=2.875,P =0.005）.Both ACLF group and CHB group had significant higher frequencies of Th22 than HC （t=2.128,P=0.037 and t=3.995,P=0.000,respectively）.The level of interferon-gamma was （25.65 ± 10.18） pg/mL and IL-22 was （24.06 ± 13.11） pg/mL in CHB patients,which were both increased significantly compared with that in HC （[12.95±6.63] pg/mL,t=5.390,P=0.000 and [15.08±8.51] pg/mL,t=2.961,P=0.004,respectively）.And the plasma levels of IL-17 and IL-22 in ACLF patients were also significantly increased compared with that in HC （t=2.654,P=0.011 and t =4.123,P=0.000,respectively）.The level of IL-22 in plasma was positively correlated with the frequency of Th22 in ACLF patients （r =0.549,P =0.012）.In a

关 键 词：T淋巴细胞 辅助诱导 TH22细胞 白细胞介素22 肝炎 乙型 慢性 肝功能衰竭 

分 类 号：R512.62[医药卫生—内科学]