HBV感染相关性肝病中调节性T淋巴细胞和辅助性T淋巴细胞17失衡的研究进展

HBV持续感染与宿主的免疫应答相关,CD4+T淋巴细胞在HBV特异性免疫应答中起重要作用。核苷和核苷酸类药物抗病毒治疗后,HBV特异性T淋巴细胞应答的恢复与CD4+T淋巴细胞亦相关。近年来新发现CD4+T淋巴细胞的2个亚群,即调节性T淋巴细胞(Treg细胞)和辅助性T淋巴细胞(Th)17,它们与HBV持续感染相关疾病的病情进展以及肝损伤相关。初步总结了Treg和Th17的分化及功能,综述了HBV持续感染相关疾病中二者的相互关系及临床抗病毒治疗后二者的变化,旨在为临床进行免疫治疗及评估预后提供帮助。     

滤泡辅助性T淋巴细胞及其在肝脏疾病发生发展中的作用

滤泡辅助性T淋巴细胞(TFH)是近年来发现的辅助B淋巴细胞产生抗体的新型CD4+T淋巴细胞亚群,与肝脏疾病的发生发展密切相关。综述了TFH的发现、分化及相关的功能分子,通过产生白细胞介素21辅助B淋巴细胞产生抗体的机制,及在慢性乙型肝炎、慢性丙型肝炎、自身免疫性肝炎、原发性胆汁性肝硬化、肝衰竭、肝移植等肝脏疾病发生发展中的作用。指出TFH可能成为治疗肝脏疾病的新型靶细胞。     

调节性T细胞和辅助性T细胞17的平衡变化在慢性乙型肝炎病毒感染中的作用

目的 研究调节性T细胞(Treg)和辅助性T细胞17(Th17)的平衡变化在慢性HBV感染中的作用.方法 应用ELISA法和流式细胞术分别对34例慢性乙型肝炎(CHB)患者、20例HBV相关慢加急性肝功能衰竭(ACHBLF)患者和20例健康对照者外周血中Treg和Th17分化相关细胞因子及外周血Th17和Treg细胞水平进行检测.计数资料应用Fisher's确切概率法,计量资料应用单因素方差分析和Tukey's多重比较检验.结果 ACHBLF组Th17分化相关因子IL-1β为(3.97±2.85) pg/mL,IL-6为(12.75±8.87)pg/mL,IL-21为(360.0±335.7)pg/mL,比健康对照组的IL-1β[(1.87±0.94)pg/mL,q=4.559,P＜0.01)、IL-6[(5.28±o.72)pg/mL,q=7.309,P＜0.01)和IL-21[(46.68±20.17) pg/mL,q=6.946,P＜0.01)均明显上调.ACHBLF组外周血Th17细胞比例明显高于健康对照组(q=3.972,P＜0.05).与健康对照组和ACHBLF组相比,CHB组Treg细胞分化相关因子TGF-β明显升高(q=4.536、5.323,均P＜0.01),外周血Treg比例也明显升高.ACHBLF组Th17细胞效应因子IL-17A水平最高,ACHBLF患者外周血Th17细胞比例与血清TBil水平呈正相关(γ=0.74,P＜0.01).结论 慢性HBV感染中,宿主免疫存在Th17和Treg失衡,ACHBLF组以Th17细胞活动为主,CHB组以Treg细胞活动为主.     

慢性乙型肝炎患者外周血中调节性T淋巴细胞、Ⅰ型调节性T淋巴细胞和辅助性T淋巴细胞17的表达特点及临床意义

目的探讨慢性乙型肝炎(CHB)患者外周血中CD4+CD25+Foxp3+(Treg)、CD4+CD25+IL-10+(Tr1)和CD4+IL-17+(Th17)的表达特点及其与CHB病情的关系。方法选取2013年1月至2014年6月解放军第一八○医院收治的轻中度CHB患者和重度CHB患者各40例,另选取同期无肝病诊断史的健康人40例为对照。分别抽取CHB患者及对照者的外周血,以流式细胞术检测外周血中Treg、Tr1和Th17表达水平,real time-PCR检测血清中Foxp3、RORγt mRNA水平,ELISA检测患者血清中TGFβ1、IL-10、IL-17表达水平。计量资料组间比较采用单因素方差分析和LSD-t检验。结果轻中度和重度CHB患者与对照组相比,Treg、Tr1和Th17的百分率,转录因子Foxp3、RORγt表达水平,细胞因子TGFβ1、IL-10、IL-17水平均明显高于健康对照组(P值均0.05);而Treg/Th17和Foxp3/RORγt值显著低于对照组(P值均0.05)。与轻中度CHB患者相比,重度CHB患者Treg、Tr1和Th17的百分率,Foxp3、RORγt表达水平,TGFβ1、IL-10、IL-17水平均显著升高(P值均0.05);Treg/Th17和Foxp3/RORγt值显著降低(P值均0.05)。结论 CHB患者中Treg(特别是Tr1)和Th17的表达失衡程度与CHB病情进展呈正相关,因此,对于CHB患者,纠正Treg(特别是Tr1)和Th17表达失衡可能是很重要的治疗措施,同时监测Treg(特别是Tr1)和Th17的表达比例改变,对于估计CHB患者病情预后、指导临床治疗有积极作用。     

辅助性T细胞17在人类免疫缺陷病毒合并结核感染致病中的作用

目的 观察HIV合并结核感染患者IL-17的表达情况,探讨Thl7细胞在HIV合并结核感染致病中的作用.方法 将54例确诊的HIV感染患者,分为单纯HIV感染组、HIV合并潜伏结核感染组和HIV合并结核感染组,采用全血胞内细胞因子染色方法,使用BD FACSCanto流式细胞仪检测各项指标,FACSDiva软件分析CD4+ IL-17+T淋巴细胞及CD4+ IFNΥ+T淋巴细胞表达情况,组间比较采用独立样本配对t检验.结果 3组患者CD4+T淋巴细胞计数及病毒载量无明显区别;CD4+ IL-17+T淋巴细胞表达百分比单纯HIV感染组为(1.40±1.01)％,HIV合并结核潜伏感染组为(1.29±0.86)％,两组比较差异无统计学意义(t=0.336,P＞0.05),但均显著高于合并结核感染组的(0.58±0.43)％(t=3.680,t=2.516,P＜0.05);3组患者之间CD4+IFNγ+T淋巴细胞表达百分比分别为(32.8±24.0)％、(40.3±21.9)％和(46.1±31.2)％,3组比较,差异无统计学意义(t=-0.939,t=-1.602,t=-0.646,均P＞0.05).结论 HIV合并结核感染患者出现明显的Th17应答下调,Th17细胞可能在HIV合并结核感染中起着重要的抗结核免疫保护作用.     

调节性T淋巴细胞与HBV感染慢性化的关系

调节性T淋巴细胞是抑制机体免疫应答,诱导机体免疫耐受的一种T淋巴细胞亚群,是近年来免疫学领域研究的热点之一。调节性T淋巴细胞功能紊乱和数量上的变化与自身免疫性疾病、感染性疾病、肿瘤免疫耐受、移植排斥以及过敏性疾病的进程和治疗密切相关。归纳了近几年调节性T淋巴细胞的表面标志、免疫机制及其与乙型肝炎发病和抗病毒治疗过程的关系。     

非小细胞肺癌患者外周血调节性T细胞和辅助性T细胞17的平衡表达特征

目的 通过检测辅助性T(Th)细胞17、调节性T细胞(regulatory T cell,Treg)相关细胞因子及特异性转录因子维A酸相关孤核受体(RORγt)和叉头转录因子3(forkhead box P3,FoxP3) mRNA的表达变化,探讨非小细胞肺癌患者外周血Treg和Th17的平衡表达特征.方法 57例非小细胞肺癌患者作为研究对象,25名健康人作为对照.通过荧光定量PCR方法检测外周血单个核细胞(PBMC)中RORγt和FoxP3 mRNA的表达.应用酶联免疫吸附方法(ELISA)检测患者外周血转化生长因子β(transforming gowth factor-β,TGF-β)和Th17相关细胞因子白介素17 A(IL-17A)、IL-6的表达.结果 Ⅳ期非小细胞肺癌患者PBMC的RORγt mRNA水平[(11.30±4.07)×10-4]高于健康组[(7.50±2.75)×10-4]及Ⅰ～Ⅲ期非小细胞肺癌患者[(5.18±2.10)×10-4](q值分别为7.53、6.82,P值均＜0.01).Ⅳ期患者血浆TGF-β水平[(69.52±10.04) pg/ml]明显高于I～Ⅲ期非小细胞肺癌患者[(42.24±16.64)pg/ml]和健康对照组[(24.51±10.96)pg/ml](q值分别为3.91、3.87,P值均＜0.05).血浆IL-6、IL-17A各组间差异无统计学意义[非小细胞肺癌Ⅳ期组、Ⅰ～Ⅲ期组、健康对照组血浆IL-17A含量分别为(25.20±4.58)pg/ml、(18.58±5.92)pg/ml、(18.93±5.24)pg/ml];[非小细胞肺癌Ⅳ期组、Ⅰ～Ⅲ期组、健康对照组血浆IL-6含量(pg/ml)分别为(39.53±11.30) pg/ml]、(42.41±12.38)pg/ml、(38.15±12.09)pg/ml(血浆IL-17A组间两两比较q值分别为1.21、1.09、1.12;血浆IL-6组间两两比较q值分别为1.19、1.76、1.06,P值均＞0.05).结论 晚期非小细胞肺癌中RORγt mRNA表达增强、外周血TGF-β表达增高,Th17以及Treg细胞可能同时参与了非小细胞肺癌的肿瘤远处转移过程,从而影响肿瘤进程.     

免疫球蛋白G4相关疾病中滤泡性辅助性T细胞/滤泡性调节性T细胞免疫平衡调控免疫球蛋白类别转换的研究进展

IgG4相关疾病(IgG4-RD)是一种免疫介导的慢性纤维炎症性疾病, 血清IgG4浓度明显升高和病变组织中IgG4+浆细胞浸润增加, 典型特征为免疫系统慢性激活和组织纤维化。其中, 滤泡性辅助性T细胞(Tfh)和滤泡性调节性T细胞(Tfr)的平衡失调在IgG4-RD的发生发展中至关重要。随着测序技术和宏基因组学研究的不断发展, 免疫球蛋白类别转换和Tfh/Tfr免疫平衡之间的关系越来越受到关注。     

免疫球蛋白G4相关性疾病患者外周血辅助性T细胞17/调节性T细胞失衡与细胞因子的关联分析

目的:探究IgG4相关性疾病（IgG4-RD）患者外周血淋巴细胞亚群表型特征及辅助性T细胞（Th）17/调节性T细胞免疫失衡与细胞因子水平的相关性。方法:收集2016年1月至2020年6月于山西医科大学第二医院风湿免疫科住院资料完整的初发IgG4-RD患者31例,留取临床及实验室资料,并选取年龄、性别匹配的30名健康体...     

特发性肺纤维化患者辅助性T细胞1/辅助性T细胞2的研究

目的 对特发性肺纤维化(IPF)患者辅助性T细胞1(Th1)/辅助性T细胞2(Th2)进行研究,探讨Th1/Th2能否反映疾病的严重性,能否预测疾病的进展.方法 入选83例IPF患者,应用酶联免疫吸附测定法检测所有受试者血清、支气管肺泡灌洗液(BALF)中γ干扰素(IFNγ)、白细胞介素-4(IL-4)水平,并进行相关性分析.结果 (1)基线资料:IPF患者血清、BALF中IFNγ/IL-4比值(0.8±0.3;0.8±0.3)较对照组(1.4±0.2;1.4±0.2)显著降低;血清、BALF中IFNγ/IL-4比值与病程、呼吸困难评分、第1秒用力呼气容积(FEV1)占预计值百分比、用力肺活量(FVC)占预计值百分比、肺总量(TLC)占预计值百分比、最大去氧饱和度、6分钟步行距离(6MWD)、CT间质纤维化评分显著相关(血清:r值分别为-0.426、-0.623、0.487、0.455、0.517、-0.491、0.263、-0.569,P值均＜0.05;BALF:r值分别为-0.434、-0.637、0.480、0.456、0.501、-0.507、0.253、-0.605,P值均＜0.05);血清中IFNγ/IL-4比值与CT磨玻璃影评分呈正相关(r=0.340,P＜0.01).(2)随访:IPF患者血清中IFNγ、IL-4、IFNγ/IL-4在糖皮质激素治疗者与非糖皮质激素治疗者间差异无统计学意义.随访6个月后的呼吸困难评分、FEV1占预计值百分比、TLC占预计值百分比、CT磨玻璃影评分、CT间质纤维化评分、IFNγ和IL-4较基线值显著恶化.血清中IFNγ/IL-4比值变化与呼吸困难评分、FVC占预计值百分比、TLC占预计值百分比、肺一氧化碳弥散量占预计值百分比、6MWD、CT间质纤维化评分的变化显著相关(r值分别为-0.297、0.462、0.315、0.353、0.420、-0.307,P值均＜0.05).结论 IPF患者血清和BALF中Th1/Th2存在失衡,Th1/Th2可能反映IPF的严重性,随访时血清中Th1/Th2的变化可能会预测IPF的疾病进展.     

慢性丙型肝炎患者外周血CD4~+调节性T淋巴细胞水平的变化及其与抗病毒疗效的关系

目的探讨慢性丙型肝炎(CHC)患者的外周血CD4~+调节性T淋巴细胞(Treg)的变化及其与抗病毒疗效间的关系。方法收集2013年1月-2016年1月于本院完成标准化抗病毒治疗与随访的85例CHC患者作为CHC组,选取40例同期健康志愿者为对照组。于治疗前,治疗12、48周,以及随访24周时采用流式细胞测定患者的外周血CD4~+Treg,并测定血清HCV RNA、AST、ALT水平。计量资料组间比较采用t检验。结果治疗前,CHC组的HCV RNA、AST、ALT及CD4~+Treg水平均显著高于对照组,差异有统计学意义(P值均0.001)。治疗12周时,CHC组85例患者中36例(42.35%)获得早期病毒学应答(EVR)(EVR组),另49例(57.65%)未获得EVR(no-EVR组),EVR组患者的HCV RNA和CD4~+Treg水平较治疗前均显著降低(t分别为39.241、8.763,P值均0.001),2组间HCV RNA、CD4~+Treg水平比较差异有统计学意义(t值分别为76.520、8.227,P值均0.001)。治疗48周时,CHC组85例患者中49例(57.65%)获得结束时病毒学应答(ETR)(ETR组),另36例(42.35%)未获得ETR(no-ETR组),ETR组患者治疗48周时的AST、ALT、CD4~+Treg及HCV RNA水平显著低于治疗前(t值分别为46.197、11.806、15.368、9.694,P值均0.001)和no-ETR组(t值分别为72.612、9.274、9.682、7.729,P值均0.001)。随访24周时,CHC组85例患者中39例(45.88%)获得持续病毒学应答(SVR)(SVR组),其中30例为获得EVR患者,32例为获得ETR患者,另46例(54.12%)未获得SVR(no-SVR组),SVR组治疗48周、随访24周的HCV RNA、AST、ALT及CD4~+Treg水平均显著低于no-SVR组(治疗48周:t值分别为117.564、17.113、10.564、4.452,P值均为0.001;随访24周:t值分别为11.196、20.997、13.384、7.900,P值均0.001)。结论 CHC患者存在外周血CD4~+Treg表达升高,抗病毒治疗可有效下调CD4~+Treg水平,减轻肝损伤。外周血CD4~+Treg检测可作为CHC发病及抗病毒疗效的评价指标。     

CD4+CXCR5+ T cells activate CD27+IgG+ B cells via IL-21 in patients with hepatitis C virus infection

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepa-titis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicularhelperT(Tfh)cells,viainterleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+T cellsintheactivationof IgG+ BcellsinCHCpatientsis not clear.
METHODS: The frequency of IgG+ B cells, including CD27?IgG+B and CD27+IgG+ B cells,the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circu-lating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The con-centrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system.
RESULTS: A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients.The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells.
CONCLUSIONS: HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21.     

Patients with chronic hepatitis C express a high percentage of CD4+CXCR5+ T follicular helper cells

Background

T follicular helper (T_FH) cells are a subpopulation of T-helper cells which regulate humoral immune responses. The role of T_FH cells in viral infection is unclear. This study examined the possible involvement of CD4⁺CXCR5⁺ T_FH cells in chronic hepatitis C (HCV) infection.

Methods

The percentages of peripheral blood CD4⁺CXCR5⁺ T_FH cells, inducible T-cell costimulator cells, and/or programmed death 1-positive CD4⁺CXCR5⁺ T_FH cells in 39 HCV-infected patients, 12 patients with spontaneously resolved HCV infection (SR-HCV), and 12 healthy controls were characterized by flow cytometry analysis. The subjects’ serum HCV RNA loads and alanine aminotransferase and aspartate aminotransferase levels were measured. The potential association of the percentage of peripheral CD4⁺CXCR5⁺ T_FH cells with clinical data was analyzed.

Results

Higher percentages of peripheral blood CD4⁺CXCR5⁺ T_FH cells were found in SR-HCV and HCV-infected patients as compared with healthy controls. Interestingly, a statistically significant negative correlation was found between the percentage of CD4⁺CXCR5⁺ T_FH cells and the HCV RNA load.

Conclusions

These data suggest that CD4⁺CXCR5⁺ T_FH cells may participate in HCV-related immune responses. Increased T_FH cells in peripheral blood may help to control HCV infection.     

慢性乙型肝炎患者外周血中T淋巴细胞亚群和CD4~+CD25~+调节性T淋巴细胞的表达水平与HBV DNA定量的相关分析

目的探讨慢性乙型肝炎(CHB)患者外周血中T淋巴细胞亚群(CD3+T、CD4+T、CD8+T、CD4+/CD8+T)和CD4+CD25+调节性T淋巴细胞(Treg)表达水平与HBV DNA定量的相关性。方法选取2012年7月-12月在兰州市第二人民医院就诊的175例HBV感染者作为研究对象,分为CHB组(63例)、HBV携带者(ASC组)(112例),以同期50例健康体检者作为对照组。采用流式细胞术检测3组患者血清中的CD3+T、CD4+T、CD8+T、CD4+T/CD8+T和CD4+CD25+Treg表达水平,实时荧光定量PCR法检测HBV DNA载量。多组间均数比较采用方差分析,进一步两两比较采用LSD-t检验,计数资料组间比较采用χ2检验;采用Pearson进行相关性分析。结果 CHB患者外周血CD4+CD25+Treg表达水平(30.97±18.78)%显著高于对照组(27.30±17.59)%,差异具有统计学意义(P0.05);与对照组相比,CHB组、ASC组的CD3+T、CD4+T淋巴细胞百分数和CD4+与CD8+T淋巴细胞百分数比值显著降低,差异均有统计学意义(P值均0.05),CD8+T淋巴细胞百分数显著升高,差异均有统计学意义(P值均0.05);ASC组和CHB组CD4+CD25+Treg表达水平与HBV DNA呈正相关(r值分别为0.501、0.682,P值均0.01)。结论 HBV感染者存在T淋巴细胞亚群比例异常,HBV DNA可以促进CD4+CD25+Treg表达水平升高,说明CD4+CD25+Treg和CD4+与CD8+T淋巴细胞比例失衡在乙型肝炎慢性化过程中发挥重要作用。     

慢性丙型肝炎患者外周血单个核细胞HCV RNA检测及其与机体免疫功能的相关性研究

目的观察慢性丙型肝炎患者外周血单个核细胞(PBMC)HCVRNA含量及其对T淋巴细胞亚群的影响,以探讨HCV感染者PBMC中HCVRNA水平及其与机体免疫功能的关系。方法采用荧光定量PCR(FQPCR)技术对128例丙型肝炎患者血清、外周血单个核细胞的HCVRNA含量进行了检测,同时检测CD3+、CD4+、CD8+、CD4+/CD8+。结果PBMC内HCVRNA阳性组与HCVRNA阴性组比较,前者CD3+、CD4+水平降低、CD8+水平增高,CD4+/CD8+比值下降大于后者,差异有显著性(P<0.05)。结论丙型肝炎病毒侵染PBMC后可加重患者的细胞免疫功能紊乱。     

老年肿瘤患者外周血CD4+CD25+调节性T细胞的检测及临床意义

目的 探讨老年肿瘤患者CD4+CD25+凋节性T细胞的变化及其与免疫衰老的关系.方法 以64例健康青年人(青年组)、52例健康老年人(老年组)和64例老年肿瘤患者(老年肿瘤组)为研究对象,采用多色荧光素标记和多参数流式细胞术,分别检测外周血中CD4+CD25high、CD4+CD25+FoxP3+和CD4+CD25+CD127low T细胞,分析和比较各组之间的差异及各指标之间的相关性.结果 以外周血中CD4+ T细胞设门,青年组、老年组和老年肿瘤组CD4+CD25high T细胞分别为(1.390±0.4]2)%、(1.729士0.247)%和(2.150±0.769)%,CD4+CD25+FoxP3+细胞分别为(1.180±0.343)%、(2.477士0.400)%和(4.980±2.177)%,CD4+CD25+CD127low T细胞分别为(5.213±0.942)%、(6.186±1.196)%和(7.194±1.538)%.3项指标均为老年肿瘤组最高,青年组最低,差异有统计学意义(P＜0.05);3项指标均呈正相关(P＜O.05).结论 CD4+CD25+调节性T细胞过量累积可能与免疫衰老及老年肿瘤密切相关.     

Increased frequency of interferon-gamma-producing peripheral blood CD4+ T cells in chronic hepatitis C virus infection

OBJECTIVES: To determine the profile of cytokine secretion by CD4+ T helper (Th) cells in chronic hepatitis C virus (HCV) infection, we used flow cytometry to determine the percentage of interferon (IFN)-gamma and interleukin (IL)-4 producing cells from CD4+ T lymphocytes in peripheral blood obtained from patients chronically infected with HCV. METHODS: Peripheral blood mononuclear cells isolated from 89 HCV infected subjects (22 asymptomatic carriers, 56 patients with chronic hepatitis, and 11 patients with liver cirrhosis) and 24 healthy controls were stained with surface CD4 and intracellular IFN-gamma and IL-4. Serum soluble IL-2 receptor (sIL-2R) levels were analyzed by ELISA. RESULTS: The frequency of IFN-gamma producing CD4+ cells in asymptomatic HCV carriers, patients with chronic hepatitis, and patients with liver cirrhosis were significantly higher than those of healthy controls (p<0.01, respectively). In contrast, the percentages of IL-4-producing CD4+ cells were very low, and there were no significant correlations with disease progression. A significant elevation in serum sIL-2R levels was found in chronic HCV infection compared to healthy controls, and serum sIL-2R levels significantly correlated with the frequency of IFN-gamma-producing cells. CONCLUSIONS: In HCV infected subjects, both serum sIL-2R and IFN-gamma are increased in chronic HCV infection no matter the stage of disease, meaning they are no different in asymptomatic carriers, patients with chronic hepatitis, and patients with liver cirrhosis, and that Th1 cytokine or Th1 cells may participate in the pathogenesis of liver damage in chronic HCV infection.     

CD4＋ T cell responses in hepatitis C virus infection

Hepatitis C virus (HCV) infection is a major cause of liver damage, with virus-induced end-stage disease such as liver cirrhosis and hepatocellular carcinoma resulting in a high rate of morbidity and mortality worldwide. Evidence that CD4+ T cell responses to HCV play an important role in the outcome of acute infection has been shown in several studies. However, the mechanisms behind viral persistence and the failure of CD4+ T cell responses to contain virus are poorly understood. During chronic HCV infection, HCV-specific CD4+ T cell responses are rela- tively weak or absent whereas in resolved infection these responses are vigorous and multispecific. Persons with a T-helper type I profile, which promotes cellular effec- tor mechanisms are thought to be more likely to experi- ence viral clearance, but the overall role of these cells in the immunopathogenesis of chronic liver disease is not known. To define this, much more data is required on the function and specificity of virus-specific CD4+ T cells, especially in the early phases of acute disease and in the liver during chronic infection. The role and possible mechanisms of action of CD4+ T cell responses in deter- mining the outcome of acute and chronic HCV infection will be discussed in this review.     

胰岛素抵抗的慢性丙型肝炎患者外周血CD4+CD25+调节性T细胞的数量及其功能

目的 了解胰岛素抵抗的慢性丙型肝炎患者外周血CD4 +CD25+调节性T细胞(Treg)数量和功能的变化.方法 筛选40例HLA-A2+慢性丙型肝炎患者(其中20例合并胰岛素抵抗),流式细胞仪检测患者CD4+CD25+Treg细胞占外周血中CD4+T细胞的频率,液闪计数仪检测对HCV特异性CD8+T细胞增殖的抑制作用,ELISA法检测IFN-y水平.统计学处理采用t检验.结果 胰岛素抵抗的慢性丙型肝炎患者外周血CD4 +CD25+ Treg细胞占CD4+T细胞的(9.5±1.9)％,明显低于慢性丙型肝炎患者的(11.2±2.2)％(t=2.615,P＜0.05).胰岛素抵抗指数(HOMA-IR)≥4患者的CD4+CD25+ Treg细胞比例为(9.0±1.8)％,明显低于HOMA-IR＜4患者的(10.8±2.3)％(t=2.413,P＜0.05).胰岛素抵抗的慢性丙型肝炎患者CD4+CD25+ Treg细胞和去除Treg的外周血单个核细胞(PBMC)共培养上清液中IFN-y为(4 050±580) pg/mL,明显高于慢性丙型肝炎患者的(2 005±330)pg/mL(t=13.705,P＜0.01).HOMA-IR≥4患者IFN-y为(5 682±986)pg/mL,明显高于HOMA-IR＜4患者的(2 819±660) pg/mL(t=7.630,P＜0.01).结论 随着胰岛素抵抗程度加重,慢性丙型肝炎患者外周血CD4+ CD25+ Treg细胞频率减低,对HCV特异性CD8+T细胞增殖的抑制作用减弱.