Lewis肺癌小鼠Th1/Th2免疫应答状态的观察

目的研究Lewis肺癌小鼠Th1/Th2免疫应答状态及其意义。方法C57BL/6小鼠16只按随机数字法分为肺癌模型组(A组)与正常对照组(B组),每组8只。A组采用Lewis肺癌单细胞悬液接种于C57BL/6小鼠右腋部皮下建立肺癌模型;B组则正常饲养未予处理。两组实验动物于实验末取血,应用酶联免疫吸附法(ELISA)检测血清中Th1细胞因子IFN-γ、Th2细胞因子IL-4浓度,并进行组间相关比较。结果A组小鼠血清中Th1相关细胞因子IFN-浓度明显低于B组小鼠,A组小鼠Th2相关细胞因子IL-4浓度明显高于B组小鼠,差异均有统计学意义(P<0.05);而FN-γ/IL-4比值A组小鼠相应低于B组小鼠,差异亦有统计学意义(P<0.05)。结论Lewis肺癌小鼠Th1/Th2免疫应答状态呈现明显Th1向Th2漂移,使肺癌细胞逃避机体免疫监视,并削弱机体的细胞免疫功能,这应是肿瘤发生发展的主要原因之一。     

Th1/Th2细胞的免疫功能变化与抗肿瘤免疫

自1986年Mosman等首先发现CD4^＋细胞（Th）具有两种不同功能的亚群细胞即Th1和Th2细胞，人们对其机体免疫反应中的作用进行了大量的体内外实验研究。近年来发现Th．细胞主要分泌IL-1，IFN-γ，LT，GM—CSF等，它主导细胞免疫应答，在抗感染器官移植排斥反应和自身免疫疾病的诱导过程中起重要作用，Th2细胞主要分泌IL-4，IL-5，IL-10，IL-13等，它主导体液免疫应答，辅助抗体生成。近来研究发现肿瘤组织多分泌Th2类细胞因子，并认为机体处于Th2细胞因子优势状态是肿瘤免疫逃逸的机理之一。因此，Th1／Th2之间的漂移能否为抗肿瘤的免疫治疗提供新型治疗方案，已成为肿瘤免疫治疗的研究热点。     

白细胞介素-13在支气管哮喘中的作用

随着免疫学和分子生物学的发展，哮喘炎症研究的重点已经移到了T淋巴细胞上。T淋巴细胞通过释放多种细胞因子，在整个炎症反应中起着至关重要的作用，近年来，对T辅助细胞功能的认识取得重大进展，机体的Th1／Th2平衡倍受研究人员关注。哮喘的发生与Th2优势应答密切相关，Th2型细胞因子如白细胞介素（IL）-4、IL-5及IL-13分泌增加，     

参麦注射液对AL化疗患者Th_1/Th_2细胞因子水平的影响

目的探讨参麦注射液对急性白血病（AL）化疗患者Th1/Th2细胞因子水平的影响。方法将20例AL患者按入院先后顺序随机分为参麦联合化疗组（试验组）和单纯化疗组（对照组）,分别于化疗前、化疗第1个疗程结束后1周采集外周血,分离血清。采用ELISA检测白介素（IL-2）,肿瘤坏死因子（INF-γ）、白介素-4（IL-4）、白介素-10（IL-10）含量。结果 2组患者经化疗后,外周血中IL-2、IFN-γ含量较治疗前均显著增加（P〈0.01）,IL-4、IL-10含量显著下降（P〈0.01）。化疗后,试验组与对照组比较,IL-2、IFN-γ含量显著增加（P〈0.05）,IL-4、IL-10含量显著下降（P〈0.05或〈0.01）。结论参麦联合化疗可以显著改善白血病化疗患者Th1和Th2细胞因子失衡状况,提高机体免疫力。     

冷束缚应激对大鼠变应性鼻炎血清中白细胞介素-4的影响

变应性鼻炎的发生是特异性Th细胞的分化发生偏移导致的Th1和Th2反应失衡,Th2细胞因子如白细胞介素（1L）-4大量表达与引发的炎性反应有关。但是,Th2优势分化发生的机制至今尚未阐明。冷束缚实验是研究心理刺激对机体影响的常用方法。     

阻塞性黄疸大鼠脾脏Th_1/Th_2细胞因子免疫状态的研究

目的　探讨阻塞性黄疸大鼠血浆及脾脏 Th1 / Th2 细胞分泌状态的变化。方法　将 80只大鼠分为对照组 ( 2 0只 )和阻塞性黄疸 A组 ( 2 0只 )、B组 ( 2 0只 )、C组 ( 2 0只 ) ,用酶联免疫吸附 ( EL ISA)法分析大鼠腔静脉血及脾静脉血干扰素 - γ( IFN- γ)、白细胞介素 ( IL) - 2、IL- 10蛋白水平的改变。结果　阻塞性黄疸组腔静脉血、脾静脉血 IFN- γ、IL- 2高于对照组 ( P<0 .0 5 ) ,而 IL- 10低于对照组 ( P<0 .0 5 )。脾静脉血 IL- 2低于腔静脉血 IL- 2( P<0 .0 5 ) ,脾静脉血 IL- 10高于腔静脉血 ( P<0 .0 5 )。结论　阻塞性黄疸大鼠存在 Th1 / Th2 细胞的免疫失衡 ,其中脾脏参与了阻塞性黄疸后机体免疫调节     

草分枝杆菌注射剂预防AECOPD作用及对COPD患者Th_1/Th_2平衡的影响

目的：探讨草分枝杆菌注射剂（乌体林斯）对COPD患者Th1／Th2细胞平衡的影响,及预防慢性阻塞性肺疾症急性加重发作（AECOPD）的临床疗效。方法：将60例Ⅱ级COPD患者随机分为治疗组和对照组,对照组予以常规治疗,治疗组在常规治疗基础上加用乌体林斯,观察乌体林斯治疗前后COPD患者外周血γ-干扰素（IFN-γ）、白介素4（IL-4）的变化,以及临床疗效。结果：治疗组IFN-γ／IL-4比值从治疗前的1．39±0．20,增加为治疗后的1．94±0．31（P〈0．01）;对照组变化不明显。治疗组显效率26．7％,总有效率96．7％,明显高于对照组的0和20％;两组临床疗效经Ridit分析,差异有统计学意义（P〈0．01）。结论：乌体林斯通过调节Th1／Th2细胞平衡,显著改善了COPD患者的免疫功能,预防AECOPD效果显著,有一定的临床推广价值。     

Th1/Th2漂移与肿瘤免疫治疗

Th1／Th2细胞是免疫应答调节中的关键环节,Th1／Th2漂移与多种疾病的发生发展密切相关。进展期肿瘤病人外周血中往往呈Th2优势状态,在抗肿瘤免疫中起重要作用的Th1免疫却受到抑制,因而设法逆转Th/Th2漂移方向,增强Th1免疫,将成为肿瘤免疫治疗的新手段。     

IL-4、IFN-γ和TCF-β1与系统性红斑狼疮的关系

目的探讨系统性红斑狼疮（SLE）与白细胞介素4（IL-4）、γ干扰素（IFN-γ）、生长转化因子β1（TGF-β1）的关系。方法采用酶联免疫吸附试验（ELISA）测定36例SLE患者和17例健康对照组的外周血单个核细胞（PBMC）培养上清液中IL-4、IFN-γ、TGF-β1的含量。结果Th1／Th2升高组的IFN-γ测值高（P〈0.05），IL4与健康对照组相比无显著差异（P〉0.05）；Th1／Th2降低组的IFN-γ测值低（P〈0.05），IL-4测值高（P〈0.05）；Th1／Th2降低组的TGF-β1高于Th1／Th2升高组，但两组相比无显著差异（P〉0．05）。结论Th1和Th2细胞极化增强均参与了SLE的发病，TGF-β1可能与SLE患者的Th1、Th2细胞极化异常有关。     

外科应激与Th1／Th2细胞因子

全身应激反应是由手术创伤和术后疼痛引起,虽然适度的应激对机体有利,但是,如果应激反应过度,就会在一定程度上对机体造成损害,甚至会削弱生理储备。近年来医学研究的热点就是,Th1／Th2型淋巴细胞。目前,已有研究显示,它与多种疾病有关,当外科应激时Th1／n12的平衡会向Th2漂移,Th2细胞因子会因过度激活和对有害物质的免疫呈现耐受状态,文章重点讨论外科手术对Th1,Th2细胞因子的影响。     

Modulation of Th1 and Th2 responses for immunotherapy

Novel therapeutic agents that differentially modulate immune responses are needed to boost protective immunity against infections and neoplasms and conversely, to suppress inappropriate immune reactions responsible for allergic and autoimmune disorders and the rejection of transplanted organs. One major concept that has guided the search for such agents asserts the existence of at least two types of CD4+ helper T-cells, Th1 and Th2 cells, that differ in their pattern of cytokine production and govern different arms of the immune response. Th1 cells produce IFN-γ, IL-2 and TNF-β and are involved in cell-mediated immune responses that are beneficial in host-defence against intracellular pathogens and malignant cells, but detrimental in mediating autoimmunity. Th2 cells secrete IL-4, IL-5, IL-9, IL-10 and IL-13, which augment antibody responses, including IgE production, and protect against helminth infestations but also cause allergy and asthma. Moreover, Th1 and Th2 responses are mutually antagonistic, such that they normally exist in equilibrium and cross-regulate each other. Alterations of this equilibrium are thought to underlie the etiopathogenesis of many immune-mediated diseases. By selectively targeting either one of these two types of polarised responses, it may therefore, be possible to achieve desired therapeutic effects without broad alterations of the immune system. The various strategies proposed in the patent literature of the last three years to modulate the Th1/Th2 balance are reviewed here. These include procedures that affect the differentiation of Th1 and Th2 cells, their production of effector cytokines and the activity of these cytokines. A profusion of new molecular targets for pharmacologic development has been identified and some attempts at therapeutic manipulation of Th1 and Th2 responses in clinical trials have been encouraging, while others have been disappointing. The emerging notion that Th1 and Th2 responses are themselves controlled by another category of T-cells, called regulatory T-cells, has offered further opportunities for immunotherapeutic intervention in autoimmunity and allergy.     

Detection of Th1, Th2 and Th17 immune responses in rats with experimental autoimmune encephalomyelitis

目的 探讨不同类型免疫反应在实验性自身免疫性脑脊髓炎(EAE)发病中的作用.方法 24只SD大鼠随机均分为EAE组和对照组,通过行为观测和大脑微观形态学确认免疫诱导的EAE模型,用ELISA法检测淋巴结和脾细胞培养上清液中IL-4、IFN-γ和血清中IgG水平,流式细胞术检测淋巴结和脾细胞中IL-17及Foxp3细胞频数.结果 与对照组相比,EAE组IgG、IFN-γ、IL-17及IL-4水平均明显增高(P＜0.05或P＜0.01).结论 Th1、Th2和Th17免疫细胞在EAE的发病均起着重要的作用.     

实验性自身免疫性脑脊髓炎大鼠Th1、Th2和Th17免疫反应检测

目的探讨不同类型免疫反应在实验性自身免疫性脑脊髓炎(EAE)发病中的作用。方法 24只SD大鼠随机均分为EAE组和对照组,通过行为观测和大脑微观形态学确认免疫诱导的EAE模型,用ELISA法检测淋巴结和脾细胞培养上清液中IL-4、IFN-γ和血清中IgG水平,流式细胞术检测淋巴结和脾细胞中IL-17及Foxp3细胞频数。结果与对照组相比,EAE组IgG、IFN-γ、IL-17及IL-4水平均明显增高(P<0.05或P<0.01)。结论 Th1、Th2和Th17免疫细胞在EAE的发病均起着重要的作用。     

Th(1)/Th(2) responses to drugs

T lymphocytes can be characterized by their pattern of cytokine secretion and be divided into type I (Th(l)/Tc(l)) and type 2 (Th(2)/Tc(2)) subsets. The involvement of type-1 or type 2-like responses in sensitization has been studied in the mouse, with reference contact and respiratory contact sensitizers. One interesting feature with certain drugs, such as beta-lactam antibiotics, is the diversity of clinical manifestations associated with immune-mediated hypersensitivity reactions in humans: immediate reactions such as urticaria, Quincke oedema and anaphylactic shock, and delayed hypersensitivity reactions, such as maculopapular rashes, allergic contact dermatitis and skin reactions of other types. In the mouse, Th(1) and Th(2) cytokines have been shown to regulate primary and secondary benzylpenicilloyl- (BPO-) specific antibody responses. Peripheral blood lymphocytes isolated from patients with a clear history of beta-lactam allergy were assessed for type-1 and type-2 phenotypes. Immediate reactions involved mixed Th(1), Tc(1), and Tc(2) responses, whereas allergic contact dermatitis involved Tc(1) and Th(1) cells. Other delayed hypersensitivity reactions to beta-lactams were restricted to Th(1) responses. It has been demonstrated that both CD4(+) and CD8(+)-lidocaine-specific T cell clones isolated from patients with allergic contact dermatitis produced IFN-gamma, even though CD8(+) clones only produce IFN-gamma, while IFN-gamma producing CD4(+) cells concomitantly produced IL-5 and IL-4. Together these data illustrate the heterogeneity of drug-specific T-cell responses.     

Th1及Th2型细胞因子与系统性红斑狼疮的相关研究

目的探讨Th1/Th2型细胞因子失衡与系统性红斑狼疮(SLE)发生及进展的关系。方法收集100例SLE患者(非活动组患者37例,活动组患者63例)及30名健康者。流式细胞仪微球捕获芯片技术(CBA)检测血清Th1及Th2型细胞因子血清白细胞介素(IL)-2、IL-4、IL-6、IL-10、肿瘤坏死因子(TNF)-α及干扰素(IFN)-γ水平。结果 (1)SLE患者组血清IL-4、IL-6及IL-10水平显著高于健康对照组(P<0.05);IL-2、TNF-α及IFN-γ与健康对照组比较差异无统计学意义(P>0.05)。(2)相关性分析显示:IL-4和IL-6与SLE疾病活动指数(SLEDAI)呈正相关,IL-2和IFN-γ与SLEDAI呈负相关,尚不能认为TNF-α及IL-10与SLEDAI有相关性。结论SLE的发生发展与细胞因子紊乱,Th2相关细胞因子占优势有关。     

Regulation of angiogenesis by Th1- and Th2-type cytokines

Angiogenesis is a complex process, where several cell types and mediators interact to establish a specific microenvironment suitable for the formation of new capillaries from pre-existing vessels. Such biological processes occur in several physiological conditions, such as embryo development and wound healing, as well as in pathological conditions, including tumours and diabetic retinopathy. T lymphocytes, neutrophils and monocytes fully participate in the angiogenic process by secreting cytokines that may control endothelial cell (EC) proliferation, their survival and apoptosis, as well as their migration and activation. Angiogenesis is the result of a net balance between the activities exerted by positive and negative regulators. This balance is conceptually very similar to that of the Th1/Th2 cells that modulate an appropriate and specific immune response. Th1 or Th2 cytokines may control angiogenesis directly, by acting on cell growth and differentiation, indirectly by inducing the release of other cytokines in the microenvironment, and by modulating the expression of specific receptors, involved in the control of angiogenic processes, such as EC proliferation and migration. In this review we will mainly discuss the role of Th1- and Th2-type cytokines in the angiogenic process, emphasizing the complexity of the cytokine and leukocyte/EC network, and highlighting the care that needs to be taken when designing new therapeutic interventions involving Th1 and Th2 cytokines.