初发系统性红斑狼疮患者外周血CD4~+CD25~+Foxp3~+和CD4~+CD25~-Foxp3~+T细胞

目的：研究初发系统性红斑狼疮患者（Systemic lupus elythematosus，SLE）外周血CD4^＋T细胞中CD25和Foxp3表达及其在SLE发病中的意义。方法：根据SLE疾病活动积分（SLEDAI）将初发SLE患者分为活动组（10例）和不活动组（11例），流式细胞仪检测治疗前后外周血CD4^＋T细胞中CD25、Foxp3和CD127表达百分率，并对其与SLE临床活动度、尿蛋白、补体和anti-ds-DNA相关性进行研究。结果：初发活动组和不活动组SLE患者CD4^＋CD25^＋Foxp3^＋T细胞表达百分率分别为（1．91％～6．75％）和（2．74％～7．01％），与正常对照（2．11％～9．90％）相比没有统计学差异（P=0．524，P=0．794）；且初发SLE患者外周血CD4^＋CD25^＋T细胞在体外增殖反应和增殖抑制功能与正常对照相比无明显差别（P=0．174，P=0．689）；外周血CD4^＋CD25^-Foxp3^＋T细胞百分率在初发活动组（3．71％～10．94％）和不活动组（2．97％～7．69％）SLE患者均比正常对照（1．01％～3．62％）显著增高（P〈0．01和P〈0．01）；而CD4^＋CD2^＋Foxp34^-T百分率在初发活动组SLE患者（1．19％～9．23％）显著低于正常对照（2．67％～11．26％）和初发不活动组SLE患者（3．73～8．27％）（P=0．039，P=0．048）；与CD4^＋CD25^＋Foxp3^＋T细胞类似，90％左右的CD4^＋CD25一Foxp3^＋T细胞不表达或低表达CD127，其百分率与anti-ds-DNA浓度呈正相关，且尽管未达到统计学意义，但激素和免疫抑制治疗后其水平下降。结论：初发未经治疗的SLE患者CD4^＋CD25^＋Foxp3^＋T细胞数量和功能无明显异常，而CD4^＋CD25^-Foxp3^＋T细胞数量增多，与SLE疾病活动相关，可能具有调节功能。     

不同结核病患者CD4^＋CD25^＋Foxp3^＋调节性T细胞表达的变化

目的分析不同结核病患者体内CD4^＋CD25^＋Foxp3^＋调节性T细胞（Tr）表达的变化,探讨其在结核病免疫中的作用。方法对33例结核病患者以及同期30例健康体检者运用流式细胞术检测其外周血CD4^＋CD25“。“和CIM^＋CD25^＋Foxp3^＋Tr表达情况。结果结核组CD4^＋CD25^high和CD4^＋CD25^＋Foxp3^＋Tr检测结果分别为（8．84±2．55）％、（6．30±1．38）％,高于对照组（7．09±1．09）％、（5．22±0．64）％,差别有统计学意义（t=3．57,4．01,P〈0．01）;痰涂阳患者CD4^＋CD25^high和CD4^＋CD25^＋Foxp3^＋Tr检测结果分别为（10．52±3．27）％、（7．18±1．77）％,高于痰涂阴患者（8．21±1．94）％、（5．97±1．06）％,两组问差别均具有统计学意义（t=2．51,2．42,P〈0．05）;初治患者和复治患者间CD4^＋CD25^high和CD4^＋CD25^＋Foxp3^＋检测结果无统计学意义（t=0．03,0．02,P〉0．05）。结论结核病患者体内CD4^＋CD25^high和CD4^＋CD25^＋Foxp3^＋Tr检测结果高于健康人群,提示患者体内存在免疫系统抑制状态。     

炎症性肠病患者外周血CD4+CD25+Treg细胞及其特异标志物Foxp3表达水平的研究

目的：通过检测炎症性肠病（IBD）不同病期患者以及对照组外周血CD4^＋CD25^＋Treg及其特异标志物Foxp3的表达，来分析与IBD疾病活动性关系，探讨CD4^＋CD25^＋Treg和Foxp3在IBD发病机制中的作用。方法：52例IBD患者和35例正常对照组分别应用流式细胞术和逆转录．聚合酶链反应（RT-PCR）检测外周血中CD4^＋CD25^＋T细胞亚群的百分率测定和外周血单个核细胞Foxp3mRNA的表达水平。结果：IBD患者外周血CD4^＋CD25^＋Treg细胞比例明显低于疾病缓解期患者和正常对照组（P〈0．01）；活动期IBD患者中使用激素和／或免疫抑制剂与未使用激素和／或免疫抑制剂结果差异有统计学意义；IBD患者外周血单个核细胞（PBMC）中Foxp3mRNA表达水平低于缓解期和正常人，差异有显著性（P〈0．05）；缓解期Foxp3mRNA水平与正常人差异无显著性（P〉0．05）；IBD患者外周血CD4^＋CD25^＋Treg细胞表达率及PBMC中的Foxp3mRNA表达水平与疾病活动指数评分呈负相关性。结论：活动期IBD患者外周血CD4^＋CD25^＋Treg细胞及Foxp3mRNA表达下调，而恢复期其表达回升，且二者呈正相关，并与临床活动评分呈负相关，因此认为CD4^＋CD25^＋Treg细胞和Foxp3可能参与疾病的发生发展，与疾病的活动性密切相关。     

成人隐匿性自身免疫性糖尿病患者CD4+CD25+T细胞的变化研究

目的：通过观察成人隐匿性自身免疫性糖尿病（LADA）患者CD4^＋CD25^＋T细胞的变化并与速发性1型糖尿病（T1 DM）比较，了解成人隐匿性自身免疫性糖尿病患者T细胞免疫功能的变化及与1型糖尿病的异同点。方法：LADA组24例，速发性T1DM18例，对照组20例，应用流式细胞技术测定3组人选者T细胞表面分子CD4、CD8、CD25、CD4^＋CD25^＋、CD8^＋CD25^＋、CD4^＋CD25^＋CD62L^＋，以百分比表示各表面分子阳性T细胞占外周血淋巴细胞的比例。结果：LADA与T1DM组CD4^＋T细胞、CD4／CD8比值明显高于健康对照组（P〈0．01），LADA与T1DM对比无差异。LADA组CD25^＋、CD4^＋CD25^＋、CD4^＋CD25^＋CD62L^＋T细胞高于健康对照组（P〈0．05），明显高于T1 DM组（P〈0．01）。T1 DM组CD25^＋、CD4^＋CD25^＋、CD4^＋CD25^＋CD62L^＋T细胞略低于健康对照组，但无统计学意义（P〉0．05）。结论：LADA患者外周血中诱导免疫耐受的CD4^＋CD25^＋、CD4^＋CD25^＋CD62L^＋T细胞较对照组升高并明显高于T1 DM患者。LADA患者胰岛B细胞功能下降较速发性T1 DM患者相对缓慢可能与CD4^＋CD25^＋T细胞的免疫保护有关。     

输血相关急性肺损伤患者外周血CD4＋CD25highFoxp3＋调节性T淋巴细胞变化的临床意义

目的检测输血相关急性肺损伤（TRALI）患者外周血CD4＋CD25highFoxp3＋调节性T淋巴细胞（Treg）的计数及其功能基因又头框蛋白3（Foxp3）mRNA的表达水平,以及探讨其与疾病预后的关系。方法收集2008年6月至2011年11月期间健康体检者（对照组,n=30）和重症监护病房收治的TRALI患者[TRALI组,n=26,TRALI组按预后又分为死亡组（n=5）和存活组（n=21）]外周抗凝血,采用流式细胞术分析各组T细胞亚群。采用四色流式细胞术以Foxp3-FITC／CD25-PE／CD4-PerCP／CD3-PC7抗体组合检测各组受试者外周血CD4＋CD25highFoxp3＋Treg的计数,比较死亡组和存活组患者外周血CD4＋CD25highFoxp3＋Treg的水平。实时荧光定量PCR技术检测特异性转录因子Foxp3mRNA的表达水平,并分析患者外周血CD4＋CD25highFoxp3＋Treg的比例与Foxp3mRNA的表达水平的关系。结果TRALI患者与对照组健康人间CD3＋T细胞、CD3＋CD4＋T细胞计数的差异无统计学意义,而CD3＋CD8＋T细胞则较对照组增加（P〈0．05）,CD4＋／CD8＋比值降低（P〈0．05）。死亡组CD3＋CD8＋T细胞比例高于存活组（P〈0．05）,C133＋T细胞、CD3＋CD4＋T细胞比例和CD4＋／CD8＋比值则低于存活组（均P〈0．05）。TRALI患者外周血CD4＋CD2.5high Foxp3＋Treg计数为（8．86±3．14）％,明显高于健康对照组（5．67±2．43）％（P〈0．05）。TRALI死亡组患者外周血CD4＋CD2shighFoxp3＋Treg计数为（11．23±3．79）％,显著高于存活组患者（7．69±3．21）％（P〈0．05）。TRALI患者外周血Foxp3mRNA的表达水平为（3．77±2．73）×10^5拷贝/ug,显著高于对照组（0．43±0．21）×10^5拷贝／μg（P〈0．05）。TRALI患者外周血CD4＋CD25highFoxp3＋Treg计数与Foxp3mRNA的表达水平呈正相关（r=0．5131,P〈0．05）。结论TRAM患者外周血CD4＋CD.5highFoxp3＋Treg和Foxp3mRNA的变化可能是导致TRALI疾病发展的关键因素之一,与?     

慢性乙型肝炎患者外周血淋巴细胞CD8+CD38+的检测意义

目的：通过测定慢性乙型肝炎患者外周血淋巴细胞CD8^＋CD38^＋的表达及门冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、凝血酶原时间（PT），旨在为治疗慢性乙型肝炎提供有用的参考指标。方法：流式细胞术检测38例慢性乙型肝炎、14例肝硬化患者外周血淋巴细胞CD8^＋CD38^＋细胞的百分率；同时测定AST、TBIL和PT。结果：（1）慢性乙型肝炎组CD8^＋CD38^＋、CD38^＋细胞均明显高于正常组（P〈0．01，P〈0．01），肝硬化组CD8^＋CD38^＋、CD38^＋细胞均明显高于正常组（P〈0．05，P〈0．05）。肝硬化组CD8^＋CD38^＋、CD8^＋细胞均明显低于慢性乙型肝炎组（P〈0．05，P〈0．05）。（2）慢性乙型肝炎轻、中、重各组之间比较，中度组CD8^＋CD38^＋高于轻度组（P〈0．05），重度组CD8^＋CD38^＋、CD8^＋、CD38^＋均高于轻度组（P〈0．05，P〈0．05，P〈0．05）；重度组CD38^＋高于中度组（P〈0．05）；肝硬化组CD8^＋CD38‘均明显低于轻、中、重各组（P〈0．05，P〈0．01，P〈0．01），肝硬化组CD8^＋低于重度组（P〈0．01）。（3）慢性乙型肝炎患者AST、TBIL、PT不正常组CD8^＋CD38^＋均高于AST、TBIL、PT正常组。结论：慢性乙型肝炎患者CD8^＋CD38^＋细胞明显升高，表明慢性乙型肝炎患者细胞免疫处于异常激活状态，并与肝功能损伤有一定的相关性。慢性乙型肝炎患者外周血淋巴细胞CD8^＋CD38^＋的测定，对病情分析和诊断有一定的临床参考价值。     

FBL3细胞在小鼠体内外诱导CD4+CD25+调节性T细胞增殖的实验研究

目的：通过小鼠体内外实验观察肿瘤细胞是否可以诱导CD4^＋CD25^＋Treg的分化增殖。方法：将小鼠的红白血病瘤细胞系FBL3接种于C57BL/6小鼠腹壁皮下,流式细胞仪检测小鼠外周血、脾脏及瘤组织CD4^＋CD25^＋Treg细胞含量,RT-PCR检测小鼠脾脏及瘤组织Foxp3 mRNA的表达;体外实验检测FBL3细胞培养上清液对小鼠脾脏CD4^＋CD25^＋Treg细胞的作用。结果：荷瘤鼠外周血CD4^＋CD25^＋Treg比例与正常鼠比较无统计学差异（P〉0.05）,但荷瘤鼠脾脏CD4^＋CD25^＋Treg比例显著高于正常对照（P〈0.01）,荷瘤小鼠脾脏组织Foxp3 mRNA的表达量明显增加;体外实验表明FBL3培养上清液促使CD4^＋CD25^＋Treg细胞比例增高,并诱导Foxp3 mRNA表达增加。结论：FBL3细胞及其分泌的可溶性物质能诱导CD4^＋CD25^＋Treg细胞的增殖,说明是肿瘤的发生促进了CD4^＋CD25^＋Treg增高。     

不同病程寻常型银屑病患者外周血中CD4+ CD25high调节性T细胞的比较与分析

目的：检测和分析不同病程寻常型银屑病患者外周血CD4^＋CD25^high调节性T细胞（CD4^＋CD25^high Treg）水平特点和意义。方法：选取进行期（70例）、稳定期（64例）和消退期（38例）寻常型银屑病患者，知情同意后，取外周抗凝全血，分离单一核细胞，采用流式细胞术检测不同病程寻常型银屑病患者外周血CD4^＋CD25^high Treg的水平，并统计分析其特点与意义。结果：进行期、稳定期和消退期寻常型银屑病患者组外周血CD4^＋CD25^high Treg与CD4^＋淋巴细胞的百分比分别为（2．86±0．9）％、（3．95±0．6）％和（4．77±0．1）％。稳定期和消退期寻常型银屑病患者组明显高于进行期组（t^＇=8．312，P〈0．01；t=10．126，P=0．000），而消退期组明显高于稳定期组（t^＇=4．588，P〈0．01）。值得注意的是，消退期寻常型银屑病患者组与正常对照组比较，差异显著，消退期组仍低于正常对照组（t=2．281，P=0．0264）。结论：不同病程寻常型银屑病患者外周血CD4^＋CD25^high Treg水平存在显著差异，提示CD4^＋ CD25^high Treg与寻常型银屑病发生和病程发展关系密切。本研究为深入研究寻常型银屑病免疫学发病机制做出了初步的尝试与探索。     

CD4+ CD25+调节性T细胞在HIV/AIDS患者中的作用及其与HIV病毒载量的相关性研究

目的 研究HIV感染者／AIDS患者外周血CD4^＋ CD25^＋ 调节性T细胞（CD4^＋ CD25^＋ regulatory Tcell，Treg）频率、功能及其临床意义。方法 选择31例HIV感染者／AIDS患者和30例健康对照者，采用流式细胞仪检测各组外周血Treg的表型和频率。采取MACS磁珠分选CD4^＋CD25^＋T细胞，利用[^3H]胸腺嘧啶掺入法检测CD4^＋ CD25^＋T细胞在特异性HIV抗原刺激下对CD4^＋ CD25-T细胞的增殖影响。结果HIV／AIDS患者组与正常对照组相比较，外周血CD4^＋ CD25^＋ T细胞频率在统计学上差异无统计学意义。与正常对照组比较，HIV感染者外周血CD4^＋ CD25^＋ T细胞频率升高，差异有统计学意义（P〈0.01）；与正常对照组比较，AIDS患者者外周血CD4^＋ CD25^＋ T细胞频率降低，差异有统计学意义（P〈0．0001）。HIV RNA病毒载量与患者外周血CD4^＋ CD25^＋ T细胞数量呈正相关性（P〈0．01）。CD4^＋ CD25^＋ T细胞具有抑制HIV特异性的CD4^＋ CD25^- T细胞的增殖作用。结论HIV感染者／AIDS患者的细胞免疫功能紊乱，CD4^＋ CD25^＋ T细胞能抑制HIV感染者／AIDS患者的HIV特异性细胞免疫反应，促进HIV病毒复制，与形成持续HIV感染有关。     

慢性乙型肝炎患者外周血调节性T细胞频率分布及功能标记的研究

目的探讨调节性T细胞（treg）细胞及功能标记在慢性乙型肝炎患者发病过程中的变化及其与疾病进展的关系。方法人组20例健康对照组、53例慢性乙型肝炎（CHB）组、24例乙肝肝硬化（LC）组患者,采用流式细胞仪检测CD4＋CD25＋Fox3＋细胞、CD4＋CD25＋CD127^low细胞、CD39＋Treg细胞、CTLA-4＋Treg细胞频率,同时检测患者临床指标。结果健康对照组、CHB组及LC组的treg细胞频率、CD4＋CD25＋CD127^low细胞频率、CI）39＋treg细胞频率差异均有统计学意义（P均〈0．01）。CHB中重度组treg细胞频率、CD4＋CD25＋CD127^low细胞频率、CD39＋treg细胞频率与轻度组间存在差异（P〈0．05,P〈0．05,P〈0．01）。CHB组内CD4＋CD25＋Foxp3＋细胞频率与ALT呈正相关（r=0．289,P〈0．05）,CD39＋treg细胞频率与ALT、AST均呈正相关（r=0．275,P〈0．05;r=0．302,P〈0．05）,CD4＋CD25＋Foxp3＋细胞频率与CD4＋CD25＋CD127^low细胞频率呈显著正相关（r=0．478,P〈0．01）。结论treg细胞频率及其功能标记频率在慢性乙型肝炎疾病进程中存在变化并与肝脏功能变化密切相关。CD39＋treg细胞可能是一群功能性的treg细胞,CD39是反应treg细胞功能较灵敏的标记。CD4＋CD25＋CD127^low细胞频率一定程度上可以代表treg细胞频率。     

慢性乙型肝炎患者外周血CD4~+CD25~+Treg与CD4~+和CD8~+ T淋巴细胞亚群的相关研究

目的:探讨慢性乙型肝炎患者外周血中CD4+CD25+调节性T细胞的含量和CD4+CD8+T淋巴细胞亚群分布,两者之间相关性及与HBV的相关性。方法:采用流式细胞术检测50例慢性乙型肝炎患者和20例健康对照者外周血中CD4+CD25high、CD4+CD25+Foxp3+Treg细胞表达及CD3/CD4/CD8 T淋巴细胞亚群,荧光定量PCR法检测HBV DNA含量。结果:慢性乙型肝炎患者外周血中CD4+CD25highTreg明显高于健康对照组(P0.01),且随HBV DNA载量增加,患者外周血中CD4+CD25highTreg细胞的水平逐渐升高。慢性乙型肝炎患者外周血中CD4+CD25+Foxp3+Treg细胞也相应增高,且与CD4+CD25highTreg细胞的变化成正相关(r=0.890,P0.001)。与健康对照组比较,患者组CD4+T细胞百分率及CD4+/CD8+比值均降低,而CD3+T细胞和CD8+T细胞百分率差异无显著性(P0.05)。CD4+CD25highTreg细胞与HBV DNA取对数后成正相关(r=0.782,P0.001),与谷丙转氨酶(ALT)成正相关(r=0.432,P0.005);与CD3+、CD4+、CD8+T细胞水平及CD4+/CD8+比值均无相关性(P0.05)。CD3+、CD4+、CD8+T淋巴细胞及CD4+/CD8+比值与HBV DNA载量之间亦无相关性(P0.05)。结论:慢性乙型肝炎患者外周血中CD4+CD25+Treg细胞增高,且与HBV的复制水平及ALT增高具有一致性,而T细胞亚群是否可作为监测CHB患者免疫状态的指标需进一步探讨。     

Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral clearance in patients with hepatitis B

Chronic activity of hepatitis B is thought to involve aberrant immune tolerance of unknown mechanism. In this study, we examined the role of CD4(+)CD25(+)Foxp3(+) regulatory T cells in disease activity and viral clearance in hepatitis B. Patients with chronic active hepatitis B (CAH) and asymptomatic HBV carriers (AsC) exhibited a significantly high frequency of CD4(+)CD25(+)Foxp3(+) T cells as opposed to that of controls and resolved HBV infection. These CD4(+)CD25(+) T cells expressed an elevated level of Foxp3 and displayed increased inhibitory activity towards both CD4(+)CD25(-) and CD8(+) effector cells. They were found to accumulate in liver biopsy tissue of CAH patients as opposed to controls. The frequency of CD4(+)CD25(+)Foxp3(+) T cells correlated positively with hepatitis B envelope (HBe) antigen status and serum HBV DNA copy numbers and had a converse relationship with HBe antibody status in patients with CAH and AsC. It was evident that in these patients, the increased frequency of CD4(+)CD25(+)Foxp3(+) T cells was associated with serum levels of transforming growth factor-beta known to promote peripheral conversion of CD4(+)CD25(-) T cells to CD4(+)CD25(+)Foxp3(+) regulatory T cells. The findings provide new insights into the role of CD4(+)CD25(+)Foxp3(+) regulatory T cells in chronic activity and viral clearance in chronic hepatitis B.     

乙肝病毒感染者外周血中CD4~+Foxp3~+T细胞亚群的表达及临床意义

目的研究外周血中3个CD4~+Foxp3~+T细胞亚群在乙肝病毒感染者外周血中频率及其可能的临床意义。方法分离来自无症状携带者(AsC)、慢性乙型肝炎患者(CHB)以及健康对照(Health)的外周血单个核细胞(PBMC),用流式细胞术分析PBMC中3个CD4~+Foxp3~+T细胞亚群占CD4~+T细胞的比例,并分析其与临床参数间的相关性,同时将CD4~+CD25~+Foxp3~+Treg作对比分析。结果CD4~+CD45RA~+Foxp3~(lo)(静息态Treg)频率在各实验组间无显著差别;CD4~+CD45RA~-Foxp3~(lo)(非Treg)频率在CHB组和AsC组间无明显差别,但两组相对Health组明显升高;CHB组CD4~+CD45RA~-Foxp3~(hi)(活动态Treg)明显高于AsC组和Health组。在CHB和AsC病例中活动态Treg与HBV病毒载量,HBeAg状态均无显著相关性。在CHB病例中活动态Treg与ALT水平不相关。结论相当比例的不具抑制功能的Foxp3~+T细胞可能混杂在CD4~+CD25~+Foxp3~+Treg的分析中,因此活动态Treg比CD4~+CD25~...     

类风湿关节炎患者外周血和滑液中CD4~+CD25~+调节性T细胞的水平变化

了解具有抑制功能的CD4+CD25+调节性T细胞(Treg)在类风湿关节炎(RA)中的水平变化。分离32例RA患者及35例正常对照者外周血和15例RA关节滑液中的单个核细胞,用荧光抗体标记细胞膜表面CD4、CD25分子和细胞内Foxp3转录因子,进行流式细胞分析,同时用RT-PCR方法测定单个核细胞中Foxp3 mRNA水平。实验发现RA外周血中CD4+CD25hT细胞比例(1.90±1.68)与健康人(1.81±1.79)无明显差异,而RA关节滑液中CD4+CD25+和CD4+CD25hT细胞含量却明显增高(14.98±12.52,8.94±9.67,P<0.01)。RA患者外周血单个核细胞中Foxp3+/CD4+T细胞比值(2.35±2.06)较正常人(7.25±3.98)明显降低(P<0.01),RA外周血中Foxp3 mRNA含量较正常人Treg减少,而RA关节液中Foxp3 mRNA含量较RA外周血更为低下(P<0.01)。RA患者存在CD4+CD25+Treg的异常改变,其外周血和关节液中具有抑制作用的Treg含量明显降低提示RA患者Treg数量减少及抑制功能下降可能是RA自身免疫反应亢强不能控制的原因之一。RA关节液中CD4+CD25hT细胞增高考虑与RA炎症反应造成T细胞过度活化有关。     

慢性乙肝患者外周血CD4CD25FOXP3 Tregs及HBV抗原特异性CTLs的检测和分析

目的: 检测慢性乙肝(CHB)患者外周血中CD4⁺CD25⁺FOXP3⁺调节性T淋巴细胞(Treg细胞)和乙肝病毒(HBV)特异性细胞毒性T淋巴细胞(CTLs)的表达及意义。方法: 收集28例CHB患者和15例健康人外周血单个核细胞标本,运用流式细胞仪对Treg细胞亚群进行定量分析,同时采用酶联免疫斑点法检测HBV抗原特异性CTLs,并结合丙氨酸氨基转移酶(ALT)和 HBV DNA的临床情况进行分析。结果: CHB组CD4⁺CD25⁺FOXP3⁺ Treg细胞的频率显著高于健康对照组 (3.14%±0.97% vs 1.95%±0.68%,P＜0.05);HBV抗原特异性CTL斑点计数为阳性(19.28±3.85)。CHB组Treg的频率与乙肝病毒载量呈正相关(r=0.831, P＜0.01),与HBV特异性CTL斑点计数值呈负相关(r＝-0.540,P＜0.01)。结论: CHB患者外周血CD4⁺CD25⁺FOXP3^＋Treg细胞表达升高并与病毒载量相关,而与HBV反应的CTLs数量呈负相关,提示Treg细胞可通过抑制细胞免疫反应影响病毒清除。     

Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease

In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed the peripheral blood from 30 patients with HCV-associated chronic liver disease and 20 healthy controls by flow cytometry for the evaluation of the Treg population [CD4?CD25hi forkhead box protein 3 (Foxp3)?], as well as the activated/effector CD4? T cells (CD4?CD25low) and IFN-γ-secreting cells. We also analysed liver biopsies of the patients by immunohistochemical evaluation of Foxp3? cells. Our results showed higher proportions of CD4?CD25low and IFN-γ? cells in the patients than in the controls. By contrast, the proportions of peripheral CD4?CD25hi cells did not significantly differ. The 11 patients displaying Foxp3? cells in the liver infiltrates showed significantly higher proportions of peripheral CD4?CD25low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3? immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.     

The opposite-direction modulation of CD4+CD25+ Tregs and T helper 1 cells in acute coronary syndromes

Different subsets of T lymphocytes have different functions in atherosclerosis advancement. T helper 1 cells and T regulatory 1 cells have been demonstrated to play opposite roles in rupture of atherosclerotic lesion. However, the role of novel subset of T regulatory cells, known as CD4+CD25+Foxp3+ T cells, remains largely unknown in coronary artery disease (CAD). In this study, we investigated the peripheral CD4+CD25+Foxp3+ T cells of patients with CAD and controls. The patients submitted were divided into three groups: stable angina pectoris (SA) group, unstable angina pectoris (UA) group and acute myocardial infarction (AMI) group. We analyzed the frequencies of peripheral CD4+CD25+Foxp3+ T cells and T helper 1/T helper 2 cells, expression of Foxp3 in CD4+CD25+ T subsets and cytokines pattern in patients and controls. We found that the reduction of CD4+CD25+Foxp3+ T lymphocytes was consistent with the expansion of Th1 cells in patients with unstable CAD. The reversed development between CD4+CD25+ Tregs and Th1 cells might contribute to plaque destabilization.     

Relations of regulatory T cells with hepatitis markers in chronic hepatitis B virus infection

To assess regulatory T cells (Treg) in chronic hepatitis B (CHB) infected patients and to evaluate the presence of a possible relation between them and hepatitis B markers, flow cytometry analysis was carried out to calculate the percentages of Tregs, Tregs secreting IL-10 and CD4(+) T cells secreting interferon-γ (IFN-γ) and enzyme-linked immunosorbent assay was used to detect hepatitis B virus (HBV) markers in 59 patients and 32 healthy controls. CD4(+)CD25(+), CD4(+)CD25(+)Foxp3(+), CD4(+)D25(high), CD4(+)CD25(high)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells and Treg cells secreting IL-10 were higher in CHB patients than in healthy controls. CD4(+)CD25(+), CD4(+)CD25(-), and total CD4(+)T cells secreting IFN-γ were generally lower in CHB patients than in healthy controls. Fair correlations were observed between CD4(+)CD25(+)Foxp3(+) T cells and alanine aminotransferase (ALT) levels and between HBsAb and both CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(high)Foxp3(+) T cells. CD4(+)CD25(+) T cells were significantly higher in CHB virus infected patients positive for HBeAg than in those negative for HBeAg and a good correlation was observed between CD4(+)CD25(+) T cells and HBeAg. Fair negative correlations were observed between CD4(+)CD25(high) T cells and both HBeAb and HBcAb. These data suggest that Tregs contribute to viral persistence. It was not possible to say that Tregs were the cause of immune suppression in this group of patients.