慢性乙型肝炎患者外周血NK细胞和T淋巴细胞计数变化及其临床意义

目的观察慢性乙型肝炎患者外周血NK细胞和T淋巴细胞数量的变化。方法在56例乙型肝炎肝衰竭、49例HBeAg阳性慢性乙型肝炎和41例乙型肝炎病毒携带者使用流式细胞仪检测外周血CD3+T细胞、CD3+CD4+T细胞、CD3+CD8+T细胞和NK(CD3-CD16+CD56+)细胞占淋巴细胞的比率(%)。结果肝衰竭患者CD3+T细胞和CD3-CD16+CD56+NK细胞计数比慢性乙型肝炎患者和乙型肝炎病毒携带者显著性降低(P0.05);慢性乙型肝炎患者CD3-CD16+CD56+NK细胞计数比乙型肝炎病毒携带者显著性升高(P0.05)。结论乙型肝炎肝衰竭患者外周血T细胞和NK细胞数量减少,而HBeAg阳性慢性乙型肝炎患者外周血T细胞数量增多。     

慢性乙型肝炎外周血中T细胞亚群和NK细胞的变化及临床意义

目的观察慢性乙型肝炎患者外周血中T细胞亚群及NK细胞含量的变化,进一步了解慢性乙型肝炎患者的免疫功能状况。方法收集48例慢性乙型肝炎患者作为实验组,其中HBe Ag阳性20例,阴性28例,选择26名健康人群作为正常对照组,采用流式细胞仪检测两组血清中CD3+T细胞、CD4+T细胞、CD8+T细胞和NK细胞的含量。结果与正常对照组比较,慢性乙型肝炎患者外周血中CD3+T细胞、CD4+T细胞和NK细胞的含量明显降低,而CD8+T细胞含量升高,差异具有统计学意义(P0.05),而HBe Ag阳性和阴性的慢性乙型肝炎患者之间的差异无统计学意义(P0.05)。结论慢性乙型肝炎患者免疫功能低下,这对患者免疫功能的判断、疾病进展、治疗及预后有一定的指导意义。     

不同病程的慢性乙型肝炎病毒感染者外周血中调节性T细胞和自然杀伤细胞的表达及相关性

目的:观察乙型肝炎病毒(hepatitis B virus,HBV)慢性感染者外周血中调节性T细胞(regulatory T cells,Tregs)和自然杀伤(natural killer,NK)细胞的表达及相关性.方法:选取HBV慢性感染患者共96例,其中慢性乙型肝炎患者42例,乙型肝炎肝硬化患者30例,HBV携带者24例,抽取外周血用流式细胞分析技术检测其Tregs和NK细胞的表达情况.同时选取健康者21例作为对照组.结果:HBV慢性感染者外周血CD4+CD25+Foxp3+Tregs占CD4+T细胞的比例整体高于健康对照组,其中乙型肝炎肝硬化患者外周血CD4+CD25+Foxp3+Tregs占CD4+T细胞的比例最高,其次为慢性乙型肝炎患者,最后为HBV携带者和健康对照组.相反,NK细胞占淋巴细胞的比例在HBV慢性感染者外周血中整体较健康对照组低,其中乙型肝炎肝硬化组表达最低,其次为慢性乙型肝炎组,最后为HBV携带者,但都低于健康对照组.进一步分析显示NK细胞的表达与Tregs呈负相关性(r=-0.3280,P0.05).结论:不同阶段的HBV慢性感染患者外周血中Tregs和NK细胞表达不同,且两者呈明显的负相关性.     

慢性乙型肝炎患者外周血及肝组织中CD4+CD25+调节性T细胞和乙型肝炎病毒特异性细胞毒性T淋巴细胞的表达及意义

目的 研究CD4+CD25+调节性T细胞和HBV特异性CTL在慢性乙型肝炎患者外周血和肝组织中的表达和临床意义.方法 流式细胞分析技术和流式细胞术细胞因子测定法(CFC)检测157例HBV感染者(包括急性乙型肝炎20例、慢性乙型肝炎115例、乙型肝炎肝硬化22例)和20例健康对照组外周血和部分肝组织中CD4+CD25+调节性T细胞和HBV特异性CTL的表达.组间分析采用t检验.结果急性乙型肝炎,慢性乙型肝炎轻、中、重度患者外周血中CD4+CD25+调节性T细胞分别为(2.87±0.94)%、(3.53±1.56)%、(4.59±2.98)%和(3.65±1.73)%,明显高于对照组的(2.36±0.60)%(t值分别为2.04、5.97、3.30和3.17,P<0.01);慢性乙型肝炎轻、中、重度和乙型肝炎肝硬化患者外周血HBV特异性CTL为(0.189土0.152)%、(0.103±0.110)%、(0.118±0.120)%和(0.098±0.101)%,明显低于急性乙型肝炎患者的(0.815±0.360)%(t值分别为10.09、11.87、9.17和8.96,P<0.01).肝组织中CD4+CD25+调节性T细胞和HBV特异性CTL的表达高于外周血.结论 CD4+CD25+调节性T细胞可能通过抑制CD8+T淋巴细胞在机体抗病毒过程中发挥重要作用.     

慢性乙型肝炎患者外周血CD8~+T细胞CD95表达的研究

目的检测慢性乙型肝炎患者外周血CD8+T细胞CD95分子的表达水平,了解CD95分子表达与炎症进展的关系。方法采集37例慢性乙型肝炎患者及健康对照者外周血,分离外周血单个核细胞(PBMCs),用流式细胞术检测外周血CD8+T细胞CD95分子的表达情况。结果高病毒载量组和低病毒载量组CD8+T细胞CD95的表达均显著高于健康对照组(P0.05);CD95的表达及CD8+T细胞频率之间存在负相关关系(r=-0.3486)。结论慢性乙型肝炎患者CD95的高表达可能促进了CD8+T细胞的凋亡,使CD8+T细胞的抗病毒作用减弱,可能与HBV持续感染、慢性乙型肝炎的形成机制有关。     

HBV相关原发性肝癌患者外周血T、NK、B细胞及胸腺功能特征

目的:观察乙型肝炎相关原发性肝癌患者(hepatitis B virus-related primary liver cancer,H B V-P L C)发生和进展过程中外周血T、N K、B细胞数量的变化,并初步探讨T淋巴细胞减少与胸腺功能的联系.方法:收集在首都医科大学附属北京地坛医院住院的73例HBV-PLC患者,50例乙型肝炎肝硬化患者(liver cirrhosis,LC),37例慢性乙型肝炎(chronic hepatitis B,CHB)患者.收集3组患者一般资料和临床生化指标.采用流式方法检测3组患者外周血中CD3~+T淋巴细胞、CD4~+T、CD8~+T、CD3-CD16~+CD56~+NK、CD3-CD19~+B的分布情况,并检测了T淋巴细胞表面CD31、CD45RA分子的表达水平.结果:与CHB和LC患者相比,HBV-PLC患者外周血中性粒细胞升高,淋巴细胞减少(P0.001);与CHB患者相比,HBV-PLC患者外周血NK细胞计数减少(P=0.011),T淋巴细胞、CD4~+T、C D8~+T、B细胞计数减少,纯真CD4~+和CD8~+T细胞表面CD31表达降低(P0.001).在肝癌Child、Okuda、BCLC分期中晚期比早期淋巴细胞计数、T、CD4~+T、CD8~+T计数均降低(P0.05).结论:随着肝癌的发生和进展,HBV-PLC患者外周血抗肿瘤免疫细胞减少,这种减少与胸腺迁出功能降低有关.     

健康老年人外周血免疫细胞功能的变化

目的 探讨健康老年人免疫细胞功能变化情况.方法 采集20例20～30岁的青年健康体检者及20例60～70岁的老年健康体检者外周血,通过PEG法检测血浆循环免疫复合物,流式细胞术检测NK、CD4+T细胞及CD8+T细胞,靶细胞K562杀伤法测定NK细胞毒.结果 老年组与青年组比,外周血循环免疫复合物水平升高;NK细胞数量无明显变化,但NK细胞毒活性明显下降;老年组CD4+T细胞与CD8+T细胞比率亦下降.结论 老年人免疫细胞功能与健康青年人比较存在一定的差异.     

CD4+CD25+Foxp3+调节性T细胞在慢性乙型肝炎患者中的作用

目的 探讨CD4+CD25+Foxp3+调节性T细胞与乙型肝炎慢性化和病毒清除之间的关系.方法 收集慢性活动性乙型肝炎(CAH)患者19例、HBV携带者(AsC)21例、HBV感染恢复者12例和健康对照者15例.通过流式细胞术分析外周血CD4+CD25+Foxp3+T细胞的表型和频率,磁珠分选(MACS)CD4+CD25+T细胞,实时荧光定量PCR方法 分析Foxp3 mRNA基因在CD4+CD25+T细胞的表达水平.统计学处理采用单因素方差分析或非参数检验.结果CAH或AsC组外周血CD4+CD25+Foxp3+T细胞频率以及CD4+CD25+T细胞中Foxp3 mRNA的表达水平显著高于健康对照组或HBV感染恢复者(F=6.8,F=3.72,均P<0.05).免疫组织化学染色发现,CAH患者肝组织Foxp3'T细胞浸润累积较对照组明显增高,但AsC较CAH减少.HBeAg阳性患者(包括CAH和AsC)CD4'CD25'T细胞频率显著高于HBeAg阴性患者(t=2.3,P<0.05),抗-HBe阴性患者显著高于抗-HBe阳性患者(t=2.4,P<0.05).CD4+CD25+Foxp3+T细胞频率与慢性乙型肝炎患者血清中HBV病毒载量存在正相关(r=0.56,P<0.01).结论 慢性乙型肝炎患者CD4+CD25+Foxp3+调节性T细胞异常与乙型肝炎慢性化和病毒清除有关.     

不同临床类型HBV感染者外周血T细胞亚群的差异

目的:观察不同临床类型HBV感染者外周血T淋巴细胞亚群的差异.方法:收集2006-9/2009-03贵阳医学院附属医院门诊及住院部慢性HBV携带者30例、慢性乙型肝炎患者47例、重型乙型肝炎患者26例以及非乙型肝炎且无影响T细胞亚群疾患者34例(高血压15例, 冠心病9例, 非甾体药物相关性消化性溃疡10例)的外周血, 用流式细胞技术检测T细胞亚群.结果:慢性HBV携带者组、慢性乙型肝炎患者组及重型乙型肝炎患者组外周血中CD3+、CD4+、CD8+ T细胞计数及CD3+、CD4+ T细胞百分数及CD4+/CD8+(计数与百分数比)均较正常对照组明显降低( P<0.05或0.01), CD8+ T细胞百分数明显升高( P<0.05或0.01), 以上改变有统计学意义, 且不同组间对比也有不同程度的统计学差异( P<0.05或0.01).结论:不同临床类型的慢性HBV感染者均存在不同程度的细胞免疫功能低下及免疫调节紊乱, 紊乱的程度与病情的进展有关.     

慢性HBV感染者外周血T淋巴细胞亚群和NK细胞活性变化

探讨慢性HBV感染者外周血T淋巴细胞亚群及NK细胞活性变化情况。应用流式细胞法检测所有研T淋巴细胞亚群和NK细胞。慢性乙肝、肝炎肝硬化和慢性重型乙肝组患者CD3 、CD4 百分率及CD4 ／CD8 比值与正常组比较均有所下降,且慢性重型乙肝组患者CD4 百分率和CD4 ／CD8 比值与正常组比较差异有显著性。各临床类型慢性HBV感染者NK细胞百分率均降低,与正常对照组比较有统计学意义。慢性HBV感染者细胞免疫功能低下。检测T淋巴细胞亚群及NK细胞活性变化对判断病变程度、指导临床治疗具有一定参考价值。     

Peripheral blood T,B, and NK cells in relation to histological hepatitis activity and fibrosis stage in chronic hepatitis C

BACKGROUND/AIMS: Many data on the pathogenesis of chronic hepatitis C have pointed to host's immune system disorders and a high variety of virus. However, there are no known criteria that could prognose the course of chronic hepatitis C infection. The analysis of T and B lymphocyte subpopulations in the peripheral blood was undertaken in patients with chronic hepatitis C of more than 6 months of duration. METHODOLOGY: Fluorescein isothiocyanate or phycoerythryne conjugated monoclonal antibodies for CD3+, CD4+, CD8+, CD19+, CD3++ HLA DR+, CD16++ CD56+ were used. The correlation between histological hepatitis activity and fibrosis (according Scheuer's scale) and the distribution of lymphocytes in the peripheral blood was sought. RESULTS: All patients with chronic hepatitis showed statistically significant increase in active lymphocytes CD3++ HLA DR+ and CD16++ CD56+ NK cells in peripheral blood. We observed the correlation between these cells and histological hepatitis activity and fibrosis. There was no correlation between the value of CD3+ and CD8+ cells and the stage of liver failure. In the early stage of chronic hepatitis C we noted decrease CD4+ cells with increase B cells CD19+. CD4+/CD8+ ratio was maintained as slightly decreased in chronic hepatitis C in favor of lymphocytes CD8+. CONCLUSIONS: The results show the correlation between peripheral blood value of activated T cell (HLA DR+) and NK cells with histological activity and fibrosis in chronic hepatitis C. Lymphocyte T (CD4+, CD8+) and B (CD19+) did not correlate with grade and stage of hepatitis C.     

外周血淋巴细胞亚群在慢性HBV感染过程中表达的变化分析

目的探讨HBV感染患者外周血淋巴细胞亚群在疾病进展过程中的表达变化。方法选取2018年1月-2019年4月在天津市第二人民医院住院的慢性HBV感染患者共132例,其中慢性乙型肝炎患者47例,乙型肝炎肝硬化患者44例,乙型肝炎肝硬化相关原发性肝癌患者41例。另选取同期健康体检者42例作为对照组。采用流式细胞术检测4组外周血淋巴细胞亚群精准计数,比较4组外周血淋巴细胞亚群的表达水平。正态分布的计量资料,组间方差不齐采用Welch方差分析,两两比较采用GamesHowell检验。非正态分布的计量资料多组间及进一步两两比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。相关性分析采用Spearman检验。结果与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD3^+、CD4^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝癌组CD8^+T淋巴细胞数量明显减少,差异有统计学意义(P<0.05);与慢性乙型肝炎组相比,肝硬化组和肝癌组CD8^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD19^+B淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝硬化组和肝癌组CD16^+CD56^+NK细胞数量明显减少,差异均有统计学意义(P值均<0.05);与慢性乙型肝炎组比较,肝癌组CD16^+CD56^+NK细胞数量明显减少,差异有统计学意义(P<0.05)。4组疾病进展与外周血CD3^+T淋巴细胞、CD4^+T淋巴细胞、CD8^+T淋巴细胞、CD19^+B淋巴细胞、CD16^+CD56^+NK细胞呈明显负相关(r值分别为-0.414、-0.503、-0.269、-0.435、-0.402,P值均<0.01)。结论随着疾病的进展,慢性HBV感染患者免疫状态发生变化。外周血淋巴细胞亚群精准计数能够反应机体的免疫状态,可作为慢性HBV感染临床病情演变、治疗效果及疾病预后的参考依据。     

肝炎肝硬化患者外周血Ⅱ型树突状细胞数量和功能变化及意义

目的 分析乙型肝炎病毒(HBV)引起的肝炎肝硬化患者外周血Ⅱ型树突状细胞(pDC2)的数量和产生α干扰素的功能，并分析其与患者淋巴细胞亚群和发生机会性感染的关系。方法 采用流式细胞分析技术对27例HBV引起的肝炎肝硬化患者进行研究，对患者外周血pDC2和淋巴细胞亚群进行检测；用体外灭活的Ⅰ型单纯疱疹病毒(HSV-1)刺激并培养外周血单个核细胞(PBMCs)，检测培养上清液中α干扰素的产量。结果 肝炎肝硬化患者pDC2的比例、细胞数和产生α干扰素的功能均降低；pDC2的数量与CDs^ T细胞及NK细胞数量高低存在正相关，而且发生机会性感染组患者的pDC2、CDs^ T细胞及NK细胞数均低于未感染组。结论 肝炎肝硬化患者外周血pDC2数量和功能下降，伴随CDs^ T细胞和NK细胞数平行降低，与肝炎肝硬化疾病进程和机会性感染有关。     

Decreased interleukin-2 receptor β chain expression by peripheral blood lymphocytes in chronic liver disease

To investigate the decrease in natural killer (NK) activity in chronic liver disease, interleukin-2 receptor beta chain (IL-2R beta) expression was assessed by peripheral blood lymphocytes (PBL) using flow cytometry and an IL-2R beta chain-specific mouse monoclonal antibody. The percentage of IL-2R beta chain-positive PBL was significantly decreased in patients with chronic viral hepatitis, liver cirrhosis and hepatocellular carcinoma in comparison with normal controls (P less than 0.01). Among chronic viral hepatitis patients, it was significantly less in those with chronic active hepatitis than in those with chronic persistent hepatitis (P less than 0.05). Two-colour flow cytometry revealed that the IL-2R beta chain was mainly expressed by CD8+ or CD16+ cells in both the controls and the liver disease patients. CD8dull+ cells (NK cells) constituted more than 60% of the CD8+ cells expressing the IL-2R beta chain. Expression of the IL-2R beta chain with CD8 or CD16 was also significantly decreased in chronic liver disease patients compared with controls. In chronic viral hepatitis, there was a significant correlation between NK activity and the percentage of IL-2R beta+ PBL (P less than 0.001, r = 0.916), as well as between NK activity and the percentage of PBL co-expressing both the IL-2R beta chain and CD16 (P less than 0.001, r = 0.850). These findings suggest that decreased expression of the IL-2R beta chain by PBL may result in diminished NK activity in chronic liver disease.     

The expression and function of NKG2D molecule on intrahepatic CD8+ T cells in chronic viral hepatitis

Summary. The natural killer (NK) cell receptor, NKG2D is a member of the c‐type lectin‐activating receptor family. It is expressed by all NK cells and by a sub‐population of CD8+ T cells. NKG2D engagement with its ligands directly activates NK cells and acts as a co‐stimulator on CD8+ T cells. Recent reports, however, have demonstrated a role for NKG2D in direct T‐cell activation in chronic inflammation. The aim of this study was to investigate the pattern of expression and the functional role of NKG2D on circulating and intrahepatic CD8+ T cells in chronic viral hepatitis. Peripheral blood lymphocytes and intrahepatic lymphocytes from 45 patients with chronic viral hepatitis (HBV and HCV) were studied. Phenotypic NKG2D expression and its functional ability to activate intrahepatic and circulating lymphocytes were analysed. Intrahepatic CD8+ T cells display increased NKG2D expression in chronic viral hepatitis in comparison with circulating CD8+ T cells. NKG2D co‐stimulates intrahepatic CD8+ T cells and hepatitis B virus‐specific CD8+ T cells. However, we could not demonstrate an ability to directly activate CD8+ T cells through the NKG2D signalling pathway alone. NKG2D is up‐regulated on intrahepatic CD8+ T cells in type B and C chronic viral hepatitis; however, its function appears to be restricted to that of a co‐stimulatory molecule.     

Immunological changes in different patient populations with chronic hepatitis C virus infection

AIM: To investigate killer inhibitory and activating receptor expression by natural killer(NK), natural killer T-like(NKT-like) and CD8+ T lymphocytes in patients with chronic hepatitis C virus(HCV) infection with elevated and with persistently normal alanine aminotransferase(PNALT).METHODS: The percentage of peripheral blood Treg cells, KIR2DL3, ILT-2, KIR3DL1, CD160, NKG2 D, NKG2 C expressing NK, T and NKT-like cells, cytokine production and NK cytotoxicity were determined by flow cytometry. Twenty-one patients with chronic HCV infection with elevated alanine aminotransferase, 11 HCV carriers with persistently normal alanine aminotransferase and 15 healthy volunteers were enrolled. RESULTS: No significant differences were observed in the percentage of total T, NK or NKT-like cells between study groups. Comparing the activating and inhibitoryreceptor expression by NK cells obtained from HCV carriers with PNALT and chronic HCV hepatitis patients with elevated alanine aminotransferase, NKG2 D activating receptor expression was the only receptor showing a significant difference. NKG2 D expression of NK cells was significantly lower in patients with elevated alanine aminotransferase. The expression of CD160, NKG2 D and NKG2 C activating receptor by CD8+ T cells were significantly lower in patients with chronic HCV hepatitis than in healthy controls and in HCV carriers with PNALT. Plasma TGF-β1 levels inversely correlated with NKG2 D expression by NK cells. In vitro TGF-β1 treatment inhibited NK cells cytotoxic activity and downregulated NKG2 D expression. CD8+ T cells from HCV carriers with PNALT showed significantly elevated expression of CD160, NKG2 D and NKG2 C activating receptors compared to chronic HCV patients with elevated alanine aminotransferase. Enhanced expression of inhibitory KIR2DL3 receptor, and decreased ILT-2 expression on NK cells were also found in chronic hepatitis C patients compared to healthy controls.CONCLUSION: Our study demonstrated a complex dysregulation of activating and inhibitory receptor expression, such as decreased NKG2 D and CD160 activating receptor expression and increased KIR2DL3 inhibitory receptor expression by NK and cytotoxic T cells and may provide further mechanism contributing to defective cellular immune functions in chronic hepatitis C. Increased NKG2 D receptor expression in HCV patients with persistently normal ALT suggests an important pathway for sustaining NK and CD8 T cell function and a protective role against disease progression.     

Decrease in CD3-negative-CD8dim(+) and Vdelta2/Vgamma9 TcR+ peripheral blood lymphocyte counts,low perforin expression and the impairment of natural killer cell activity is associated with chronic hepatitis C virus infection

BACKGROUND/AIMS: As chronic hepatitis C virus (HCV) infection is associated with impaired natural killer (NK) cell cytotoxicity, we examined the phenotypes and perforin expression of peripheral blood lymphocytes, as well as the effect of interferon-alpha2b (IFN-alpha2b) therapy. METHODS: Thirty-three patients had chronic hepatitis C, and of them 12 had been on IFN-alpha2b treatment. Eleven individuals had been treated earlier with IFN-alpha2b and completely cured, and eight were HCV carriers with persistently normal serum alanine aminotransferase. Three-colour flow cytometry was used to measure the percentage of CD3(+/-)CD8+, CD3+CD4+, gammadeltaTcR+, Vdelta2 TcR+, Vgamma9 TcR+, Vdelta1 TcR+, CD3-CD16+, CD3-CD56+, CD19+ and perforin-positive cells. NK cell activity was assessed by single cell cytotoxic and flow cytometric assay. RESULTS: Patients with chronic hepatitis C showed an impaired NK cytotoxicity, decreased percentage of CD3-negative-CD8dim-positive (NK subtype) and Vgamma9/Vdelta2 TcR+ as well as perforin-positive T lymphocytes, compared to controls and to those who were cured from HCV infection. IFN-alpha2b increased NK cell cytotoxicity and the percentage of perforin-positive lymphocytes. CONCLUSIONS: Our findings suggest that in chronic HCV infection a decreased percentage of CD3(-)CD8+, Vgamma9/Vdelta2 TcR+ and perforin-positive T cells and simultaneous decreased peripheral NK activity may contribute to the impaired cellular immune response and the chronicity of the disease.     

中国乙型肝炎患者外周血淋巴细胞亚群频率参考值范围

目的 调查中国乙型肝炎患者外周血淋巴细胞亚群频率参考值范围.方法 利用流式细胞术检测2846例乙型肝炎患者和117例健康人群外周血淋巴细胞亚群数值,调查我国健康人群和乙型肝炎人群的参考值范围.结果 调查了16～60岁健康人群和HBV感染相关的急性肝炎、慢性肝炎、重型肝炎和肝硬化人群外周血CD3+T淋巴细胞、CD3+CD...     

Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology

Cytokines released by infiltrating T cells may contribute to the hepatic injury in chronic hepatitis. Therefore, we characterized peripheral blood- and liver-infiltrating T cells from patients with chronic hepatitis of different etiology and determined the T cell phenotypes and the cytokine release. Liver tissue and peripheral blood-derived T cells from patients with autoimmune hepatitis and primary biliary cirrhosis predominantly expressed CD4-molecules and the α- and β-chains of the T cell receptor (TCR). In chronic viral hepatitis B and C, liver- and blood-derived T cells were preferentially CD8+ T cells expressing the αβ TCR. Mitogenic stimulation with irradiated Daudi lymphoma cells and phytohemagglutinin led to a strong release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) by T cells in patients with chronic hepatitis and in healthy controls. T cells from patients with primary biliary cirrhosis and some patients with autoimmune hepatitis showed a significantly higher secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10) than T cells from patients with chronic viral hepatitis or healthy controls. Histologic inflammatory activity did not correlate with the amount of cytokines released after mitogenic activation. In conclusion, liver tissue and peripheral blood T cells of patients with autoimmune hepatitis and primary biliary cirrhosis were dominated by CD4+ TCR αβ+ T helper/inducer cells, whereas in chronic viral hepatitis an enrichment of CD8+ TCR αβ+ cytotoxic/suppressor T cells was observed. In addition, analysis of the cytokine release showed that T cells in autoimmune and chronic viral liver diseases secreted high amounts of IFN-γ and TNF-α, cytokines predominantly secreted by T_hl-like cells. The secretion of the T_h2 cytokines. IL-4 and IL-10, however, was increased in autoimmune hepatitis and primary biliary cirrhosis. These data show that in autoimmune and chronic viral liver diseases different functional T cell subsets are activated.