慢性乙型肝炎患者外周血Treg/Th17比率的检测及其与肝功能的相关性研究

目的:探讨Treg、Th17细胞及Treg/Th17比率与肝功能的相关性,以便更好地反映慢性乙型肝炎(CHB)患者肝脏免疫炎症。方法:收集41例HBeAg阳性CHB患者、29例HBeAg阴性CHB患者和20例健康志愿者的外周血,采用流式细胞术检测Treg细胞(CD4+CD25highCD127low)和Th17细胞(CD3+CD8-IL-17+)的频数;采用酶联免疫吸附试验(ELISA)检测血清TGF-β1水平;采用全自动生化仪检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)、直接胆红素(DBil)等指标。结果:CHB患者Treg和Th17细胞的频数明显高于健康对照组(P<0.05),Treg/Th17比率低于健康对照组(P<0.05)。CHB患者Treg细胞频数与TBil、DBil和AST呈正相关(P<0.05),Th17细胞与以上指标均无相关性(P>0.05)。HBeAg阳性CHB患者Treg/Th17比率与TBil、DBil和ALT呈正相关(P<0.05),且随病情进展Treg/Th17比率呈上升趋势(P>0.05),TGF-β1则明显升高(P<0.05);HBeAg阴性患者Treg/Th17比率与ALT呈负相关(P<0.05)。综合治疗平均2个月后,HBeAg阳性患者Treg/Th17比率仍与TBil保持正相关(P<0.05)。结论:Treg细胞和Treg/Th17比率与CHB患者的肝功能具有良好相关性。监测Treg、Th17细胞及其比率,有助于反映CHB患者肝组织的免疫炎症。     

不同类型HBV感染者外周血Treg/Th17细胞的变化及意义

目的:探讨不同类型HBV感染者外周血中CD4+ Foxp3+ Treg/Th17细胞的变化及意义.方法:选取15例急性乙型肝炎(Acute Hepatitis B,AHB)患者、40例慢性乙型肝炎(Chronic hepatitis B,CHB)患者、40例无症状携带者(Asymptomatic HBV carriers,AsC)及30例健康对照者,分别采用流式细胞术、RT-PCR和ELISA检测外周血CD4+ Foxp3+ Treg/Th17细胞百分率、核转录因子foxhead winged-helix box protein 3 (Foxp3)/retinoid-related orphan receptor gamma-t (RORγt) mRNA的表达以及血浆转化生长因子-β1(Transforming growth factor-31,TGF-β1)/IL-17的水平.结果:AHB组患者CD4+ Foxp3+ Treg/CD4+T细胞百分率、Foxp3 mRNA及TGF-β1水平与正常对照组相比无明显差异(P＞0.05);而CD4+ IL-17 +/CD4+T细胞百分率、RORγtmRNA及IL-17水平与正常对照组相比明显升高,差异有统计学意义(P＜0.05).CHB组患者CD4+ Foxp3+ Treg/CD4+T细胞百分率、Foxp3 mRNA、TGF-31水平及CD4+ IL-17 +/CD4+T细胞百分率、RORγt mRNA、IL-17水平与正常对照组相比均明显升高,差异有统计学意义(P＜0.05);与正常对照组相比,AsC组患者CD4+ Foxp3+ Treg/CD4+T细胞百分率、Foxp3 mR-NA、TGF-β1水平及CD4+ IL-17 +/CD4+T细胞百分率、RORγt mRNA、IL-17水平无明显差异(P＞0.05).结论:在不同类型HBV感染者外周血中Treg/Th17细胞失衡,Treg/Th17细胞可能与HBV感染的状态有关.     

慢性乙型肝炎患者核苷(酸)类似物治疗前后外周血中Treg和Th17细胞及其相关细胞因子水平的变化

目的 观察慢性乙型肝炎(CHB)患者应用核苷(酸)类似物(NA)抗病毒治疗前后外周血中Treg、Th17细胞及其相关细胞因子水平的变化.方法 采用流式细胞术,检测44例NA治疗12周的CHB患者外周血Treg(CD4+ CD25high CD127low)和Th17(CD3+ CD8-IL-17+)细胞频率.ELISA检测血清IL-10、TGF-β1、IL-17及IL-23水平.各组间采用Mann-Whitney U检验,治疗前后采用Wilcoxon配对T检验.结果 完全应答的14例患者的Treg细胞频率、IL-10、TGF-β1和IL-23水平及Treg/Th17比率较治疗前明显下降(Z=-2.691,-2.417,-2.237,-2.291,-2.291,P均＜0.05),Th17细胞频率及IL-17水平略有增加.部分应答的11例患者的Treg细胞频率、IL-10、TGF-β1和IL-23水平较治疗前明显下降(Z=-1.988,-2.934,-2.756,-2.803,P均＜0.05),Th17细胞频率及IL-17水平略有增加,Treg/Th 17比率略有下降.无应答的15例患者的Treg和Th17细胞频率、IL-10、TGF-β1、IL-23、IL-17水平及Treg/Th17比率较治疗无明显变化.HBV DNA下降≥2 log拷贝/ml及ALT恢复正常时,Treg细胞频率与细胞因子IL-10、TGF-β1和IL-23水平较治疗前明显下降(P均＜0.05).Treg细胞频率与HBV DNA及ALT水平三者之间具有一定的相关性.结论 NA抗病毒治疗前后,CHB患者Treg和Th17细胞频率及IL-10、TGF-β1、IL-23、IL-17水平均发生变化;治疗后获得满意应答的CHB患者Treg细胞频率、IL-10、TGF-β1、IL-23水平及Treg/Th17比率明显下降,Th17细胞及IL-17水平继续上升;且以上变化与病毒学应答及生化学应答有关.     

慢性乙型肝炎患者外周血Th17细胞/调节性T细胞比值变化的意义北大核心CSCD

目的测定慢性乙型肝炎(CHB)患者外周血CD4+CD25+Foxp3+调节性T细胞(Treg)和CD4+IL-17+T细胞(Th17细胞)频率及其相关细胞因子的变化,并探讨Th17/Treg平衡在CHB发病过程中的作用。方法选取CHB住院患者(CHB组)60例,其中35例轻中度CHB患者(CHB-LM),25例慢性重型肝炎患者(CSHB),同时选取21位健康体检者作为正常对照组(HC)。流式细胞术检测外周血中Th17和Treg的细胞频数,双抗体夹心ELISA检测血清中IL-17、IL-23、IL-10及转化生长因子β1(TGF-β1)的表达水平。结果与HC组相比,CHB患者外周血Th17细胞频率及其相关细胞因子IL-17、IL-23浓度明显增高,差异有统计学意义(P<0.05);Treg频率及其相关细胞因子IL-10及TGF-β1浓度明显增高。Th17/Treg比值变化显示,与HC组相比,在CHB组中该比例明显升高,具有显著性差异,且与CHSB组相比,在CHB-LM组中该比值明显降低。结论 Th17细胞/Treg的失衡是造成慢性乙型肝炎病程演变的重要因素,检测Th17细胞/Treg比值变化对疾病发展的早期预测有一定价值。     

成人哮喘患者Treg/Th17细胞失衡与呼出气一氧化氮的相关性研究

目的:探讨成人哮喘患者Treg/Th17细胞失衡与呼出气一氧化氮(FeNO)的相关关系。方法:募集成人哮喘患者17例,慢性咳嗽非哮喘患者16例。所有患者均检测FeNO值,并用ELISA法检测血浆IL-17的表达水平,流式细胞术检测外周血中Treg、Th17细胞占CD4~+T淋巴细胞比例。比较两组患者FeNO水平的差异及其与Treg/Th17的相关关系。结果:与慢性咳嗽组相比,哮喘组血浆IL-17浓度升高(P<0.05)、外周血Th17/CD4~+T细胞比值升高(P<0.001)、FeNO水平升高(P<0.001)、Treg/Th17细胞的比值降低(P<0.001),而Treg/CD4~+细胞比值无明显变化(P>0.05)。哮喘组FeNO值与外周血Treg/CD4~+T细胞比值无明显相关性,而与Th17细胞占CD4~+T淋巴细胞比例呈正相关(r=0.663,P=0.01),与Treg/Th17细胞比值呈负相关(r=-0.757,P=0.002)。结论:哮喘患者FeNO水平升高与Treg/Th17失衡有关,主要与Th17细胞表达升高有关。     

过敏性紫癜患儿Th17、Treg 细胞及IL-17、IL-23 水平的测定

目的:观察过敏性紫癜(Henoch-Schonlein purpura,HSP)患儿急性期及恢复期Th17、Treg 细胞及IL-17、IL-23水平变化,以便更好地认识HSP 的免疫学发病机制,为HSP 的治疗提供帮助。方法:采用流式细胞术(Flow cytometry,FCM)检测HSP 患儿65 例和健康对照组儿童30 例外周血中Th17 细胞和Treg 细胞比例;采用双抗体夹心酶联免疫吸附(ELISA)法测定其血浆中IL-17、IL-23 水平。结果:HSP 急性期组Th17、Th17/ Treg 细胞及IL-17、IL-23 水平高于正常对照组(P<0.05),恢复期组较急性期组降低(P<0.05),但仍高于正常对照组(P<0.05)。HSP 急性期组Treg 水平低于正常对照组(P<0.01),恢复期组较急性期组升高(P<0.01),但是仍低于正常对照组(P<0.01)。单纯型、腹型和其他类型HSP 患儿Th17、Treg、Th17/ Treg 及IL-17、IL-23 水平相同(P>0.05)。HSP 急性期患儿Th17 细胞比例与IL-17 水平呈正相关(r =0.880,P<0.01);HSP 急性期患儿IL-23 水平与Th17 细胞比例、IL-17 水平呈正相关(r =0.838 或r =0.877,P<0.01)。结论:Th17、Treg、Th17/ Treg、IL-17 和IL-23 共同参与HSP 的发病,但在单纯型、腹型和其他类型中的水平无明显差异,值得深入研究。     

高压氧对新生儿黄疸疗效、TGF-β、IL-17、Treg和Th17的影响

目的 探讨高压氧对新生儿黄疸疗效、转化生长因子β(TGF-β)、白介素17(IL-17)、调节性T细胞（Treg和辅助性T细胞17(Th17)的影响。方法 选择2018年7月至2020年9月在西北妇女儿童医院治疗的新生儿黄疸患儿202例，通过随机数字表方法将患儿分为观察组和对照组，每组各101例。对照组采用蓝光照射治疗，观察组在对照组基础上采用高压氧治疗。比较两组患儿的疗效、胆红素水平、TGF-β、IL-17、Treg、Th17、Th17/Treg及不良反应。结果 两组各92例患儿纳入最终分析。观察组治疗后总有效率明显高于对照组（P=0.022）。观察组治疗后直接胆红素（DBIL）、总胆红素（TBIL）、间接胆红素（IBIL）和经皮黄疸指数（TCB）水平均低于对照组（P<0.001）。观察组治疗后TGF-β和IL-17水平均低于对照组（P<0.001）。观察组治疗后Treg水平高于对照组（P<0.001）,Th17和Th17/Treg水平均低于对照组（P<0.001）。观察组不良反应总计明显少于对照组（P=0.036）。结论 高压氧能够增加新生儿黄疸的疗效，降低...     

血清25-羟基维生素D、Th17/Treg细胞失衡与新生儿缺氧缺血性脑病预后的相关性研究

目的:探究缺氧缺血性脑病(HIE)患儿血清25-羟基维生素D[25(OH)D]及Th17/Treg细胞水平的变化及其与患儿预后的关系。方法:选取2019-01-2021-01本院收治的79例HIE患儿(HIE组),根据临床分度分为中度组(46例)和重度组(33例);根据HIE组患儿神经发育随访情况将其分为神经发育正常组(52例)和不良神经发育组(27例)。选取同时期本院健康新生儿79例为对照组。利用流式细胞术检测外周血中Treg细胞比率、Th17细胞比率并计算Th1/Th17细胞比率;采用酶联免疫吸附(ELISA)法检测血清中25(OH)D、白细胞介素(IL)-17、IL-23及IL-10和转化生长因子-β(TGF-β)水平。Cox风险比例回归模型评估HIE患儿预后不良的影响因素;采用Pearson法分析Th17/Treg与25(OH)D之间的相关性。结果:与对照组相比,HIE组血清中IL-17、IL-23水平、Th17细胞比率及Th17/Treg细胞比率较高(P<0.05),25(OH)D、IL-10、TGF-β水平、Treg细胞比率较低(P<0.05);与中度组相比,重...     

IL-35对慢性阻塞性肺疾病患者Treg/Th17平衡的影响北大核心CSCD

目的:观察IL-35在慢性阻塞性肺疾病(COPD)患者外周血中的表达及其对CD4^(+)CD25^(+)CD127^(dim/-)Treg和辅助性T细胞17(Th17)的调控作用。方法:选取44例COPD患者和25例健康对照者,分离血浆和外周血单个核细胞(PBMC),ELISA检测血浆IL-35水平,流式细胞术检测PBMC中CD4^(+)CD25^(+)CD127^(dim/-)Treg和Th17水平,计算Treg/Th17。重组人IL-35刺激COPD患者PBMC,流式细胞术检测CD4^(+)CD25^(+)CD127^(dim/-)Treg和Th17比例,ELISA检测培养上清中IL-10、IL-17和IL-22水平,RT-PCR检测FoxP3和RORγt mRNA表达。磁力分选COPD患者PBMC中的CD4^(+)CD25^(+)CD127^(dim/-)Treg,重组人IL-35刺激后与自体PBMC共培养,CCK-8检测细胞增殖。结果:与对照组相比,COPD组血浆IL-35水平降低[(108.20±12.13)pg/ml vs(133.30±22.91)pg/ml,t=5.980,P<0.000 1],CD4^(+)CD25^(+)CD127^(dim/-)Treg比例降低[(4.71±1.00)%vs(6.07±1.03)%,t=5.362,P<0.000 1],Th17比例升高[(2.97±0.72)%vs(2.28±0.61)%,t=4.060,P=0.000 1],Treg/Th17降低(1.69±0.60 vs 2.86±0.91,t=6.279,P<0.000 1)。重组人IL-35刺激后,CD4^(+)CD25^(+)CD127^(dim/-)Treg比例升高(P=0.000 2),Treg/Th17升高(P=0.015 0),而Th17比例无明显变化(P=0.391 0),培养上清中IL-10水平升高[(145.10±24.40)pg/ml vs(123.50±24.11)pg/ml,t=4.520,P<0.000 1],而IL-17和IL-22水平均无明显变化(P>0.05),FoxP3 mRNA表达显著升高(1.27±0.19 vs 0.96±0.10,t=7.600,P<0.000 1),而RORγt mRNA表达无明显变化(P=0.447 0)。重组人IL-35刺激COPD患者分选的CD4^(+)CD25^(+)CD127^(dim/-)Treg免疫抑制活性增强。结论:IL-35主要通过提高CD4^(+)CD25^(+)CD127^(dim/-)Treg比例和活性影响Treg/Th17平衡,在COPD过程中可能发挥免疫保护作用。     

Treg/Th17平衡在巨细胞病毒感染发病机制中的作用

目的:研究调节性T细胞(Treg/Th17)细胞失衡在巨细胞病毒感染(CMV)免疫调节机制中的作用。方法:将CMV感染患儿按诊断标准分为激活感染组与潜伏感染组,同时设立正常对照组,采用流式细胞术(FCM)分析各组外周血Treg、Th17的百分比,并计算Treg/Th17比值;同时采用ELISA和RT-PCR法检测Treg主要相关因子(IL-10、Foxp3)和Th17主要相关因子(TGF-β、IL-17、IL-6、IL-23及ROR-γt)表达水平。结果:与对照组比较,CMV感染后Treg细胞百分率降低,Th17细胞升高,致Treg/Th17比值下降(P<0.05);CMV感染后两组间比较,激活感染组Treg/Th17比值和Treg主要相关因子表达水平下降更明显,而Th17主要相关因子表达水平显著上调,差异均有统计学意义(P<0.05)。结论:Treg/Th17平衡参与了CMV感染发病免疫机制,并可能与病毒潜伏-激活状态相关。     

Th17和Treg细胞以及其相关细胞因子在慢性丙型肝炎以及丙型肝炎肝硬化病人外周血中的变化及意义

目的：〖HTSS〗研究Th17和Treg细胞以及其相关细胞因子在慢性丙型肝炎以及丙型肝炎肝硬化病人外周血中的变化及意义,以探讨其在慢性丙型肝炎及丙型肝炎肝硬化发病中的作用。 〖HTH〗方法：〖HTSS〗用流式细胞和ELSIA技术检测慢性丙型肝炎及丙型肝炎肝硬化病人外周血Th17和Treg细胞表达率以及IL 6、IL 10、TGF β、IL 17血清学水平,分析上述指标在健康对照组和慢性丙型肝炎组以及肝硬化组之间的差异。 〖HTH〗结果：〖HTSS〗慢性丙型肝炎病人的Th17细胞表达率(133%±030%)以及IL 6［(810±242）ng/L］、IL 17［(1670±473）ng/L］血清水平明显高于健康对照组Th17 细胞表达率(114%±019%)以及IL 6［(670±172）ng/L］、IL 17［(1229±188）ng/L］血清水平,P＜005;丙型肝炎肝硬化组和慢性丙型肝炎组病人外周血的Treg细胞表达率(621%±076%,589%±085%)明显高于健康对照组的Treg细胞表达率（551%±059%）,P<005;丙型肝炎肝硬化组病人Th17/Treg的比值（019±002）明显低于慢性丙型肝炎组（022±003）和健康对照组（021±003）,P<005;丙型肝炎肝硬化组外周血IL 10水平［（1621±376）ng/L］和TGF β水平［（515±083）ng/L］显著高于慢性丙型肝炎组［（1436±278）ng/L;（447±087）ng/L］和健康对照组［（1401±301）ng/L;（443±098）ng/L］,P<005。 〖HTH〗结论：〖HTSS〗Th17和Treg细胞以及其相关细胞因子参与了丙型肝炎慢性化和肝硬化的进程,Th17和Treg细胞以及其相关细胞因子在丙型肝炎慢性化和肝硬化的治疗和预防方面可能具有重要的意义。     

Increased Th17 cells and interleukin-17 contribute to immune activation and disease aggravation in patients with chronic hepatitis B virus infection

T helper17 (Th17) cells have been demonstrated to participate in the pathogenesis of hepatitis B virus (HBV) associated liver damage. However, the contribution of Th17 cells to immune activation and disease aggravation in patients with HBV infection is not fully clear. In this study, we investigated the Th17 cells frequencies and interleukin-17 (IL-17) mRNA expressions in peripheral blood mononuclear cells (PBMCs), intrahepatic IL-17-positive cells accumulation, as well as serum IL-17 levels in asymptomatic chronic HBV carriers (AsC), and patients with chronic hepatitis B (CHB) and HBV related acute-on-chronic liver failure (ACLF). Furthermore, the dynamic changes of Th17 cells frequencies and IL-17 concentration in different prognostic ACLF patients were observed. As result, the intrahepatic and peripheral Th17 cells and serum IL-17 concentration were both significantly higher in CHB and HBV related ACLF patients than that in AsC and normal control groups, and increased gradually with immune inflammation aggravation from AsC, CHB to ACLF. Moreover, in ACLF patients, peripheral Th17 cells frequencies were positively correlated with international normalized ratio (INR) and model of end-stage liver disease (MELD) score. Especially the survival patients had an initially lower Th17 cells frequencies and IL-17 levels which gradually decreased following condition improvement as compared with higher baseline level followed by gradually increasing trend in the non-survivals. In conclusion, Th17 cells can be contributed to the immune activation and disease aggravation in patients with chronic HBV infection. This may places Th17 cells as a potential blocking target for controlling CHB and ACLF.     

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~...     

The correlation between T helper type 17 cells and clinical characters in Chinese paediatric patients with chronic hepatitis B

Interleukin (IL)‐17‐mediated immune response has been shown to play a critical role in inflammation‐associated disease. However, its role in the pathogenesis of chronic hepatitis B virus (HBV) in paediatric patients remains unknown. We investigated the frequency of T helper type 17 (Th17) cells and evaluated the association between the Th17 and clinical characters in paediatric patients with chronic hepatitis B (CHB). The frequency of Th17 cells was detected by flow cytometry analyses from 65 paediatric patients with CHB and nine healthy controls. The degree of hepatic inflammation was graded using the histological activity index (HAI). Compared with healthy controls, the frequency of Th17 cells in peripheral blood was significantly higher in paediatric patients with CHB. The proportion of Th17 cells was higher in the patients with higher HAI score (G2–G3) compared to those subjects with lower HAI score (G0–G1), but the frequency of Th17 cells had no correlation with serum HBV DNA loads or alanine aminotransferase levels. Compared with the younger age group (age 1–6 years), Th17 cell frequency was higher in the older age group (age 7–18 years). Peripheral Th17 cell frequency is associated closely with inflammation activity of liver tissues in paediatric patients with CHB.     

The ratio of Th-17 to Treg cells is associated with survival of patients with acute-on-chronic hepatitis B liver failure

Both T-helper 17 cells (Th-17) and CD4(+)CD25(+) regulatory T cells (Tregs) play important roles in the pathogenesis of hepatitis B virus (HBV) infection. Recent studies have suggested that Th-17 and Treg cells are increased in patients with chronic hepatitis B (CHB). This study further characterizes Th-17 and Treg cells in the blood of HBV-associated acute-on-chronic liver failure (ACLF) patients, and aids our understanding of how the two subsets of CD4(+) T cells affect each other and contribute to survival. Blood samples were obtained from 30 patients with HBV-associated ACLF, 30 patients with CHB, and 30 normal controls (NC). The frequencies of Th-17 and Treg cells were determined by intracellular cytokine staining analysis. To observe the suppressive function of Tregs, purified CD4(+)CD25(+) Tregs from peripheral blood mononuclear cells (PBMCs) were co-cultured with CD4(+)CD25(-) T cells for 48?h, and then IFN-γ and IL-17A from the supernatants were measured by ELISA. We found that both Th-17 and FoxP3(+) Treg cells were increased in ACLF patients. IL-17A secretion by CD4(+) T cells was not regulated by Treg cells, even though Tregs exhibited significant inhibition of IFN-γ production. Most importantly, the ratio of Th-17 to Treg cells was associated inversely with the survival of ACLF patients. These findings provide new information regarding the pathogenesis of HBV-associated ACLF, and the ratio of Th-17 to Tregs may represent a potential prognostic marker for the disease.     

DAPT 调节Treg / Th17 细胞免疫平衡抑制动脉粥样硬化

目的:观察Notch 信号抑制剂分泌酶抑制剂( DAPT)对动脉粥样硬化小鼠病理改变及Treg/ Th17 细胞免疫平衡的影响。方法:将24 只ApoE 基因敲除C57BL 小鼠随机分为空白组、模型组和DAPT 组。空白组用普通饲料饲养,模型组和DAPT 组用高脂饲料饲养。饲养5 周后,DAPT 组小鼠以100 mg/ (kg•d)皮下注射DAPT(溶于DMSO 中),其余两组皮下注射等量DMSO。5 周后,采用病理染色分析各组小鼠动脉病理改变,ELISA 检测血浆中IL-17 水平,采用流式细胞术检测各组小鼠脾脏Treg/ Th17 细胞比例。结果:HE 染色结果显示,模型组有明显粥样斑块形成和泡沫细胞形成,DAPT 组动脉病变程度比粥样动脉硬化模型组明显减轻。正常组、模型组和DAPT 组各组血浆中IL-17 水平分别为(293.94±28.59)、(454.05±172.68)和(335.40±89.57)pg/ ml;DAPT 降低AS 小鼠血浆IL-17 水平(P<0.05)。空白组、模型组和DAPT 组各组小鼠Treg 细胞百分比分别为(3.0±0.56)%、(2.54±0.38)%和(4.73±0.64)%;DAPT 降低AS 小鼠血浆IL-17 水平(P<0.05)。空白组、模型组和DAPT 组各组小鼠Th17 细胞亚群分别为(3.46±0.23)%、(4.52±0.85)% 和(1.38±0.37)%。结论:DAPT 降低AS小鼠血浆IL-17 的水平,抑制Th17 细胞亚群分化,而促进Treg 细胞分化,通过改变Treg/ Th17 细胞疫平衡从而减轻动脉粥样硬化。     

Tim‐3 regulates inflammatory cytokine expression and Th17 cell response induced by monocytes from patients with chronic hepatitis B

Tim‐3 is expressed on monocytes/macrophages and is involved in the regulation of inflammatory responses. The aim of this study was to determine the effect of Tim‐3 on inflammatory response triggered by peripheral monocytes from patients with chronic hepatitis B (CHB). Tim‐3 expression on peripheral monocytes and frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) derived from CHB patients were detected. Followed by lipopolysaccharides (LPS) activation of circulating monocytes from CHB patients, expression of inflammatory cytokines including TNF‐α，IL‐1β and IL‐6 were examined in the presence and absence of Galectin‐9 which is the ligand for Tim‐3. Subsequently, after purified CD4+T cells were cocultured with LPS‐activated monocytes from CHB patients in the presence of anti‐Tim‐3 antibody, percentage of Th17 cells and production of IL‐17 were measured. Tim‐3 expression was significantly upregulated and closely correlated to the frequency of Th17 cells in patients with CHB. Expression of TNF‐α，IL‐1β and IL‐6 increased significantly in monocytes stimulated with LPS and Galectin‐9, compared to LPS stimulation alone. LPS‐activated monocytes from CHB patients could drive differentiation of memory CD4+T cells to Th17 cells. However, under the blockade of Tim‐3 signalling by anti‐Tim‐3 antibody, percentage of Th17 cells and production of IL‐17 decreased significantly. Our results demonstrate that upregulated expression of Tim‐3 on circulating monocytes accelerates inflammatory response by promoting production of inflammatory cytokines and Th17 responses in CHB.     

不同类型乙肝病毒感染者HBV抗原特异性T细胞免疫应答

目的 了解不同类型HBV感染人群T细胞对HBV抗原蛋白免疫应答的差别及特征.方法 76例研究对象分为四组,乙肝携带者组和既往乙肝感染患者组、急乙组、慢乙组,酶联免疫斑点法检测其外周血T细胞对HBV特异性抗原蛋白HBsAg、HBcAg和HBeAg免疫应答.结果 (1)携带者组对HBeAg的反应频率较高,而既往感染者对HBcAg和HBeAg的反应频率较高.急乙组和慢乙组对三种蛋白的反应频率无差别.(2)急乙组和慢乙组对HBsAg的反应频率明显高于既往感染组.急乙组、慢乙组和既往感染组对HBcAg的反应频率明显高于携带者组.对HBeAg的反应频率各组间无差别.(3)慢乙组对HBcAg的反应强度明显高于HBsAg.既往感染组患者对三种蛋白的反应强度依次为HBcAg＞ HBeAg＞ HBsAg.急乙组和携带者组对三种蛋白的反应强度无差别.(4)对HBsAg的反应强度从高到低依次为急乙组＞慢乙组＞携带者组和既往感染组.对HBcAg的反应强度是急乙组和慢乙组和既往感染组明显强于携带者组.对HBeAg的反应强度,急乙组高于慢乙组,其余各组间无差别.结论 急乙、慢乙和既往感染者对HBcAg的T细胞免疫反应为主,而携带者以HBeAg的T细胞免疫反应为主.