不同级别胶质瘤患者术前外周血Th1/Th2细胞因子的表达

目的:分析不同级别脑胶质瘤患者手术前外周血Th1/Th2细胞因子表达变化。方法:选择近期住院的脑胶质瘤患者63例,在治疗前采用ELISA方法进行外周血IFN-γ、IL-2、IL-4和IL-10浓度检测。结果:胶质瘤组外周血IL-4和IL-10浓度均明显高于对照组,而前者外周血IFN-γ、IL-2浓度及IFN-γ/IL-4比值则显著低于后者(P<0.05或P<0.01)。高级别组(Ⅲ~Ⅳ级)外周血IL-4和IL-10浓度均明显高于低级别组(Ⅰ~Ⅱ级),而前者外周血IFN-γ、IL-2浓度及IFN-γ/IL-4比值则显著低于后者(P<0.05或P<0.01)。结论:脑胶质瘤患者可能有Th2优势表达,与恶性程度有一定关系。     

阿托伐他汀对Lewis大鼠实验性自身免疫性心肌炎作用的研究

目的： 探讨阿托伐他汀对实验性自身免疫性心肌炎(EAM）大鼠Th1/Th2偏离的影响及对EAM的治疗价值。方法: 6-8周雄性Lewis大鼠31只，其中8只作为正常对照；23只以猪心肌肌球蛋白免疫制成EAM模型，免疫后随机分为阿托伐他汀大剂量（10 mg·kg^-1·d^-1）组、小剂量（1 mg·kg^-1·d^-1）组和未治疗组，连续用药 21 d。第 21 d，行超声心动图检测；取心肌组织，观察大体及镜下炎症程度；ELISA检测血浆IL-2、IL-4、IL-10及IFN-γ等细胞因子水平,并以IFN-γ/IL-4比值作为Th1/Th2偏离方向指标。结果: 阿托伐他汀使EAM大鼠心室肥厚减轻，LVEDd降低，射血分数增加；心脏重量/体重比值及炎症程度分级显著降低；Th1型细胞因子(IFN-γ, IL-2)水平降低，Th2型细胞因子水平(IL-4, IL-10)升高。3组间TC、TG及HDL-C水平未见明显差异。结论: 阿托伐他汀使Th1/Th2平衡向Th1方向偏离，抑制EAM炎症反应。表明阿托伐他汀的免疫调节效应及在自身免疫病治疗中的应用前景。     

高迁移率族蛋白B1与原因不明复发性流产患者Th1/Th2平衡的相关性

目的 探讨HMGB1和Th1/Th2型细胞因子在原因不明复发性流产（URSA）患者外周血中的表达及相关性研究。方法 纳入2019年6月至2020年6月期间在深圳市妇幼保健院妇科就诊的100例URSA患者为URSA组,分别于免疫治疗前、后采集患者外周血。以同期100例体检健康妇女为对照组。比较两组外周血中Th1、Th2细胞比例、Th1/Th2比值、IL-2、IFN-γ、IL-4和IL-10和HMGB1的表达。比较治疗后不同妊娠结局URSA患者细胞因子和HMGB1表达水平。采用Pearson相关分析法分析细胞因子和HMGB1的相关性。结果 URSA治疗前与治疗后和对照组相比、妊娠成功组与失败组相比,IL-2、IFN-γ和HMGB1均升高,IL-4和IL-10均降低（P<0.05）;URSA治疗前与对照组比,Th1细胞比例、Th1/Th2值升高,Th2细胞比例降低（P<0.05）。HMGB1与IL-2和IFN-γ呈正相关,与IL-4和IL-10呈负相关（均P<0.01）。结论 URSA的发病与Th1/Th2细胞平衡向Th1方向偏移有关,HMGB1可能参与了Th1/Th2失衡...     

CCK-8对KLH免疫小鼠脾细胞Th1/Th2平衡的影响

目的： 探讨八肽胆囊收缩素（CCK-8）对Th1/Th2平衡的调节作用。方法: 给予BALB/c小鼠钥孔戚血蓝蛋白（KLH）免疫同时体内给予不同剂量的CCK-8,酶联免疫吸附试验(ELISA)检测其脾细胞培养上清中Th1型细胞因子γ-干扰素(IFN-γ)、白细胞介素-2（IL-2）和Th2型细胞因子白细胞介素-4（IL-4）、白细胞介素-5（IL-5）水平,逆转录聚合酶链式反应(RT-PCR)法检测脾细胞中IFN-γ、IL-2、IL-4、IL-5 mRNA表达;ELISA法检测血清中Th1型抗KLH抗体IgG2a和Th2型抗KLH抗体IgG1水平。结果: ①KLH免疫使小鼠脾细胞分泌Th1/Th2型细胞因子水平明显增高,mRNA表达增高,KLH免疫同时给予CCK-8可使脾细胞培养上清中IFN-γ、IL-2含量进一步增加和IFN-γ、IL-2mRNA表达增高,而使IL-4、IL-5含量降低,IL-4、IL-5 mRNA表达减低和降低IL-4/IFN-γ比值。②KLH免疫小鼠血清中IgG2a、IgG1发生不同程度增高,CCK-8可使其血清中IgG1水平减低而使IgG2a水平增高。结论: CCK-8可促进KLH免疫小鼠体内Th1反应,使Th2优势反应向Th1方向转变。     

CpG ODN对rHBsAg免疫小鼠Th1/Th2型免疫应答的影响

目的：初步探讨CpC寡脱氧核苷酸(CpG ODN)与重组乙型肝炎表面抗原(rHBsAg)联合免疫小鼠的Th1／Th2型免疫应答效应。方法：BALB／c小鼠经后腿胫骨前肌免疫2次，ELISA法检测血清乙型肝炎表面抗体(抗-HBs)IgG亚类IgG2a/IgG1的比值；生物活性法检测脾细胞诱生上清中的IFN-γ和IL-2含量；ABC-ELISA法检测小鼠血清中IL-4、IL-10及IL-12含量。结果：加CpG ODN组与单独注射rHBsAg组相比：抗-HBs IgG亚类IgG2a／IgG1比值明显高；Th1型细胞因子IFN-γ和IL-2的表达增强，抑制Th2型细胞因子IL-4和IL-10的产生。结论：CpCODN能够明显增强rHBsAg免疫小鼠Th1型抗体亚类IgG2a的产生，并且诱导Th1型细胞因子的表达，抑制Th2型细胞因子的表达。     

MiR-143在Lewis肺癌小鼠外周血中的表达及其对Th1/Th2平衡的影响

目的 利用小鼠Lewis肺癌移植肿瘤模型探究肺癌疾病进展过程中外周血微小RNA的表达及其对Th1/Th2平衡的调控作用。方法 利用Real-time PCR实验检测血浆中miR-143、miR-217、miR-195和miR-615的表达水平;用酶联免疫吸附实验（ELISA）检测小鼠外周血血清IFN-γ、IL-2、IL-4和IL-10表达水平,用流式细胞术检测小鼠脾脏CD4+IFN-γ+Th1细胞及CD4+IL-4+Th2细胞比例,测量并统计荷瘤小鼠皮下接种部位肿瘤体积及肺部转移性结节;分离小鼠外周血CD4 T细胞,检测转录因子T-bet和GATA3的表达。结果 与Normal组相比,LCC组小鼠外周血血清miR-143表达水平显著上升,miR-217、miR-195和miR-615表达水平没有明显变化。与Normal组相比,LCC组小鼠外周血Th1相关细胞因子表达水平及脾脏Th1细胞比例下降,而Th2相关细胞因子表达水平上升,且Th1/Th2比率显著下降。而Anti-miR-143组Th1相关细胞因子及Th1细胞比例升高,且Th2相关细胞因子比例下降。与LCC组相比,Anti-miR...     

急性MCMV感染对小鼠脾Th1/Th2/Th17细胞亚群分化的影响

目的:在整体水平观察小鼠巨细胞病毒(MCMV)感染对小鼠脾Th1/Th2/Th17细胞亚群分化及其主要的效应性细胞因子(IFN-γ、IL-4、IL-17A)表达的影响.方法:建立MCMV感染模型,8只BALB/c小鼠分别于接种MCMV Smith株后3天和14天各处死4只;另设8只接种唾液腺匀浆的模拟感染小鼠作为对照.用空斑形成试验测定肝、脾和唾液腺组织病毒滴度;流式细胞术检测脾T淋巴细胞中Th1(CD4+ IFN-γ+)、Th2(CD4+ IL-4+)、Th17(CD4+IL-17A+)细胞比例,双抗体夹心ELISA法检测脾细胞培养上清中病毒特异性IFN-γ、IL-4、IL-17A水平.结果:MCMV感染早期肝、脾和唾液腺组织中病毒呈低水平复制,而感染后14天仅在唾液腺组织呈高水平复制;Th1细胞比例及病毒特异性IFN-γ主要在MCMV感染早期呈显著升高(P ＜0.01);Th2细胞及IL-4均无明显表达及改变;Th17细胞及病毒特异性IL-17A则主要在感染后14天升高(P＜0.05).结论:MCMV感染早期,机体通过上调Th1细胞分化比例及IFN-γ的表达发挥抗病毒效应,而MCMV诱导Th17细胞分化及IL-17A的高表达可能是MCMV感染致宿主特异性细胞免疫功能失调并逃避机体特异性细胞免疫攻击的原因之一.     

安脑片对aGVHD小鼠Th1/Th2细胞的调节作用

目的:观察中药安脑片对aGVHD小鼠的Th1/Th2细胞的调节作用。方法:清洁级BALB/c雄性小鼠作为供鼠,以清洁级C57BL/6雌性小鼠为受鼠,建立aGVHD模型;C57BL/6小鼠在移植前进行60Co全身照射,剂量为9.0 Gy,照射后4小时内尾静脉输注BALB/c雄性小鼠的骨髓细胞8×107个/只+脾细胞8×107个/只。造模成功后,随机分为安脑片组和空白组。移植后第30天杀鼠取材,取眶静脉血并制备肝脏标本,ELISA法检测小鼠血清IFN-γ及IL-10水平,免疫组化法检测肝脏组织IFN-γ及IL-10的阳性表达。结果:安脑片组小鼠血清IFN-γ的表达治疗前为(9.67±0.88)pg/ml,治疗后降至(4.81±0.87)pg/ml,IL-10的表达在治疗前为(3.81±0.55)pg/ml,治疗后升至(8.16±0.92)pg/ml。免疫组化的结果也显示小鼠肝脏组织IFN-γ及IL-10的表达改善明显,治疗后小鼠IFN-γ的表达评分降为1.27±0.46,IL-10的表达评分升至3.73±0.46,与治疗前相比差异显著(P=0.000)。结论:安脑片可有效改善小鼠aGVHD效应并调节Th1/Th2细胞因子的平衡。     

米非司酮通过增强母-胎界面Th1型偏移导致流产

目的：探讨米非司酮对母胎界面Th1/Th2型细胞因子动态平衡的影响.方法：将63例早孕期妇女随机分为2组,一组一次服用米非司酮200 mg,另一组为对照组,收集其蜕膜组织.应用免疫组化法,评价Th1型细胞因子（IL-2、IFN-γ）、Th2型细胞因子（TGF-β2、IL-4）的表达.结果：正常妊娠时,在母-胎界面Th2型细胞因子（IL-4）以及TGF-β2的表达较高;Th1型细胞因子（IL-2、IFN-γ）的表达较低,尤其是IL-2.服用米非司酮后,蜕膜Th1型细胞因子（IL-2、IFN-γ）表达显著升高;而母-胎界面Th2型细胞因子（IL-4）以及TGF-β2的表达无明显变化.结论：米非司酮打破了正常妊娠时母胎界面Th2型免疫优势;显著升高Th1型细胞因子（IL-2、IFN-γ）表达,形成了Th1型免疫偏离,导致流产的发生.     

慢性乙肝、肝硬化和肝癌患者Th1/Th2细胞因子检测及临床应用

目的:应用流式微球技术(cytometric bead array,CBA)技术检测慢性乙肝、肝硬化及肝细胞性肝癌(hepatic cellular cancer,HCC)患者血浆中Th1/Th2细胞因子水平,探讨其临床应用。方法:选择慢性HBV感染者71例,HBV阳性肝硬化患者33例,HBV阳性肝癌患者25例,用CBA方法检测其血清中Th1类细胞因子TNF-α、IFN-γ、IL-2,Th2类细胞因子IL-4、IL-5、IL-10的表达情况。结果:肝癌患者血清中Th1类细胞因子TNF-α、IFN-γ、IL-2,Th2类细胞因子IL-5表达显著高于慢性乙肝和肝硬化患者,而IL-4、IL-10在三组患者中的表达无显著性差异。结论:肝癌患者机体强势分泌Th1类细胞因子,处于高免疫反应状态。检测乙肝患者Th1/Th2类细胞因子对于肝病慢性化的进展成为一项新的临床预测指标。     

The Th1/Th2 paradigm

The Th1/Th2 paradigm provides a useful model for understanding the pathogenesis of several diseases, as well as for developing novel immunotherapeutic strategies. Here, Sergio Romagnani examines Th1/Th2 polarization in the context of associated pathophysiological conditions.     

Th1/Th2 balance in infection

Cytokines produced by T helper (Th) cells are of critical importance for the outcome of many infectious diseases. Producing the right set of Cyokines in response to an infectious agent can be a matter of life or death. The Th1/Th2 dichotomy, although an oversimplification has proven useful in the analysis of immune responses to infections. In some infectious diseases, most notably leishmaniasis or infections with gastrointestinal helminths, one Th subset is indispensable for clearing the infection, whereas the opposite Th subset is detrimental. More frequently, both Th1 and Th2 responses are required at different time points to effectively eradicate an infectious agent. The granuloma responses to eitherMycobacterium tuberculosis orSchistosoma mansoni provide illustrative examples and are discussed in this review. There is accumulating evidence for frequent coexpression of Th1 and Th2 Cyokines during the in vivo immune response to infections. The mechanisms by which infectious agents modulate Th1/Th2 phenotype development are summarized here. Finally, we review here the current evidence for cytokine imbalances induced by infections as pathogenic or protective factors in autoimmunity and allergy.     

Th1, Th2, and Th3 cytokine alterations in major depression

BACKGROUND: Many studies have shown that the balance between Th1 cytokines and Th2 cytokines plays a role in modulation of cellular responses in the brain during psychological stress and psychiatric disorders. The Th3 cytokine, transforming growth factor beta-1 (TGF-beta1), has been shown to regulate the balance between Th-1 and Th-2 cytokines. However, the role of TGF-beta1 in the psychoimmunology of depression has never been explored. METHODS: A total of 40 depressed patients and 80 normal controls were recruited. The plasma levels of IFN-gamma, IL-4, and TGF-beta1 were studied at the time of admission and 8 weeks after antidepressant treatment. RESULTS: The proportion of patients who showed immunoreactivity to IFN-gamma and IL-4 in the plasma, and the plasma IFN-gamma/IL-4 ratio, were significantly higher in depressed patients than in controls. The IFN-gamma/TGF-beta1 ratio was also higher in depressed patients, and TGF-beta1 levels showed a significant negative correlation with the HDRS depression scale. After treatment, TGF-beta1 level increased significantly, and the IFN-gamma/IL-4 ratio decreased significantly, in the patient group. However, Th1 changes in male and female showed different trend such as Th1 arm was decreased after the treatment in all male, whereas it was increased in premenopausal age women. LIMITATIONS: Replication and extension using a larger sample size are required. CONCLUSIONS: The Th1 and Th2 cytokine imbalance was observed in subpopulation of depressed patients. TGF-beta1 seemed to play a role in the pathophysiology of depression in this population. Moreover, antidepressant treatment was found to affect the Th1/Th2 balance through the action of TGF-beta1.     

Stability of Th1 and Th2 populations

Using an in vitro model for the development of IFN-y-producIng(Th1) and IL-4-produclng (Th1) cells from CD4 T lymphocytesexpressing a transgenlc TCR, we show that IL-12 and IL-4 arethe most potent stimuli for the differentiation of naive T cellsto effector populations. When combinations of cytokines arepresent during T cell priming, the effect of IL-4 Is dominant.Furthermore, differentiated Th1 cells can be converted intoIL-4 producers by exposure to IL-4, but the Th2 phenotype Isnot reversible. The stability of Th2 populations may limit theability to regulate Th2-domlnant responses In pathologic situations.     

Th1、Th2、Th17型细胞因子与糖尿病肾病相关性的研究

糖尿病肾病(diabetic Nephropathy,DN)是导致终末期肾脏病(end-stage renal disease,ESRD)的最主要病因,因此,早期诊断和治疗是糖尿病肾病的诊治要点。但目前糖尿病肾病的确切发病机制尚未完全明确,糖尿病肾病的发生发展与血流动力学改变和代谢的紊乱、氧化应激和炎症等多种因素有关,而细胞因子在2型糖尿病及其相关肾脏并发症的病因、发病机制中也起着重要的作用,各种细胞因子的识别将为糖尿病肾病的诊治提供新的潜在治疗靶点。文章就Th1、Th2、Th17型细胞因子与DN相关性的研究作了综述。