慢性乙型肝炎的Th细胞亚群及相关细胞因子网络失衡

辅助性T细胞(helper T cell,Th细胞)是根据功能分类的一个T细胞亚群,根据所分泌细胞因子的不同,Th细胞可分为Th0、Th1、Th2和Th3 4种亚群,其中研究最多的是Th1和Th2两个亚群.Th1/Th2细胞及其细胞因子网络的调节对维持机体正常的免疫功能至关重要.乙型肝炎病毒(HBV)感染机体后,多种因素影响Th细胞增殖并且调节其亚型比例,细胞因子网络受到破坏,在细胞因子介导下便可造成肝脏等组织和器官的损害,直接或间接地影响到乙型肝炎发病及其转归.     

Th22在肝炎发病机制中的作用

辅助性T淋巴细胞的概念最早由Coffman和Carty[1]及Mosmann等[2]在1986年提出,是机体重要的免疫调节细胞,根据其产生细胞因子的不同可分为不同的功能亚群,即Th1和Th2,分别参与调节细胞免疫和体液免疫,它们之间可相互调节,影响免疫应答的格局.     

Th1/Th2细胞因子与肝病关系的研究新进展

辅助T细胞(helperTcell,Th)是指能帮助B细胞分化成抗体产生细胞和放大细胞免疫应答的一个细胞群,它表达CD4而不表达CD8。Th活化后可释放细胞因子,调节T细胞、B细胞、单核细胞和其他免疫细胞活性,根据产生细胞因子的不同,Th可分为Th1、Th2及Th0三型,机体对细胞内与细胞外抗原的免疫应答主要受Th1和Th2调节。活化的Th1产生白细胞介素(IL)-2、干扰素(IFN)-γ和其他免疫效应分子,可促进T细胞应答,增强细胞免疫应答,抑制抗体产生、诱导迟发型超敏反应;活化的Th2释放IL-4及IL-10等细胞因子,可使B细胞活化、促进抗体产生。Th细胞是免疫应答的中心细胞,它不但是机体免疫应答的启动细胞,而且其活性对整个免疫应答具有调节作用,如果没有Th的活化,机体就会处于无能状态。Th1与Th2之间存在相互制约或促进作用,细胞因子组成一个复杂的分子网络,参与调节炎症反应以及器官功能的自我稳定,细胞因子介导的免疫应答在肝细胞炎症坏死、病毒清除及病毒持续存在等方面的免疫机制中均起着中心作用。     

泡球蚴病患者血清中Th1/Th2型细胞因子水平的观察

近年来研究发现,Th1和Th2细胞产生的细胞因子在病程转归中具有重要作用,可反映宿主机体内免疫应答的反应类型。本文对泡球蚴病(AE)患者血清中的各种细胞因子进行了检测,以了解Th1/Th2型细胞因子在AE患者细胞免疫调节中的作用及临床意义。     

肺癌患者血清中IL-12、IL-10水平测定及其临床意义

正辅助性T(Th)细胞在机体免疫应答过程中具有重要调节作用。细胞因子谱与细胞免疫功能有重要关系,正常情况下,细胞因子Th1和Th2处于相互制约、转化的平衡状态,当Th1/Th2细胞群发生亚状态,机体免疫力就会遭到破坏,发生病理     

慢性肝炎

T细胞亚群功能调节和小儿慢性肝炎（综述）——陈怡等（福建福州市传染病医院肝病研究所350025）；《国际流行病学传染病学杂志》2007，34（4）：256-257[Th1 和Th2细胞分别介导机体的细胞免疫和体液免疫，它们来自一个共同的前体细胞ThO，在不同的细胞因子、抗原等因素的影响下，可发生Thl与Th2的转换。     

Th1/Th2漂移与支气管哮喘的免疫治疗

Th1/Th2细胞在不同的细胞因子、抗原等因素的影响下，可发生Th1/Th2的转换，研究表明在支气管哮喘（哮喘）的发生机制中，Th2细胞分化明显增多，而Th1细胞数目减少。因此，促进Th1反应，抑制Th2反应的免疫治疗是治疗哮喘的重要部分。目前许多调节Th1/Th2失衡的免疫治疗方法已取得一些进展。     

Th1细胞在活动性乙型肝炎肝硬化和慢加急性肝衰竭发病中的作用

HBV感染所致的肝细胞损伤及肝组织炎症与机体细胞免疫密切相关,其中细胞毒性T淋巴细胞(CTL)和巨噬细胞作为主要的效应细胞,与病毒的清除和肝细胞的损伤直接相关[1].CD4+Th细胞是机体免疫应答中的重要组成成分,在调节CTL细胞和巨噬细胞的免疫效应中发挥关键作用[1-2].本研究以Th1和Th2细胞及其功能性细胞因子为切入点,以活动性乙型肝炎肝硬化及慢加急性肝衰竭患者肝组织为主要研究对象,探讨Th1和Th2细胞在上述两种疾病发病机制中的作用.     

Th17细胞与肝脏及相关疾病的研究进展

人体免疫类型包括特异性（获得性）免疫和非特异性（固有）免疫,其中特异性免疫主要由T淋巴细胞和B淋巴细胞参与。辅助性T细胞（Th细胞）由CD4＋T细胞分化成熟而来,在机体细胞免疫及体液免疫中发挥重要作用。1986年Mosmann等,将Th细胞根据其分泌的细胞因子以及在机体免疫中的不同作用,把Th细胞分为Th1和Th2细胞亚群［1］。在IFN-γ及IL-12的协同作用下,CD4＋T细胞分化成熟为Th1细胞,并分泌肿瘤坏死因子α（TNF-α）、γ干扰素（IFN-γ）、白介素（IL-2）等,在抗细胞内感染和细胞免疫反应中起到重要的作用。     

结核分枝杆菌感染与Th1/Th2免疫应答的研究进展

CD4+T淋巴细胞据其产生的细胞因子不同可分为Th1和Th2两类细胞,其中Th1细胞介导Th1免疫反应;Th2细胞介导Th2免疫反应.在一定条件下,Th1免疫反应可转化为Th2免疫反应.结核病发病时表现为Th1免疫应答受抑和(或)Th2免疫应答亢进,并且 Th1免疫反应抑制程度与结核病严重程度相一致,随着结核病的治愈,Th2为主的免疫反应转化为Th1为主的免疫反应.CpG DNA能在动物体内激发Th1相关的免疫反应,抑制Th2相关免疫反应.因此,CpG DNA可能在防治结核病方面发挥重要作用.     

Role and development of TH1/TH2 immune responses in the lungs

The development of T helper 1 (Th1) and Th2 responses is dependent on the cells and early signals of the innate immune system. Following inhalation of pulmonary pathogens, lung antigen-presenting cells (APCs) ingest the microbe, begin to process antigen, and migrate to peripheral lymphoid tissues (i.e., LALNs). It is in the lymph node that the APC-T cell interaction takes place; therefore, the microenvironment of the lymph node significantly influences the developing T cell response (Th1 vs Th2). Several factors can determine the nature of the T cell response, including cytokines, chemokines, microbial virulence factors, and dendritic cell phenotype. A shift in the Th1/Th2 balance in the lungs can result in chronic infection, allergic disease, and immunopathology. This review discusses the mechanisms of developing Th1/Th2 pulmonary responses, the counterregulation of Th1/Th2 immunity, and the consequences of immune deviation in the lungs.     

T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function

T helper (Th) cells can be categorized according to their cytokine expression. The differential induction of Th cells expressing Th1 and/or Th2 cytokines is key to the regulation of both protective and pathological immune responses. Cytokines are expressed transiently and there is a lack of stably expressed surface molecules, significant for functionally different types of Th cells. Such molecules are of utmost importance for the analysis and selective functional modulation of Th subsets and will provide new therapeutic strategies for the treatment of allergic or autoimmune diseases. To this end, we have identified potential target genes preferentially expressed in Th2 cells, expressing interleukin (IL)-4, IL-5, and/or IL-10, but not interferon-γ. One such gene, T1/ST2, is expressed stably on both Th2 clones and Th2-polarized cells activated in vivo or in vitro. T1/ST2 expression is independent of induction by IL-4, IL-5, or IL-10. T1/ST2 plays a critical role in Th2 effector function. Administration of either a mAb against T1/ST2 or recombinant T1/ST2 fusion protein attenuates eosinophilic inflammation of the airways and suppresses IL-4 and IL-5 production in vivo following adoptive transfer of Th2 cells.     

Cytokine detection by ELISPOT: relevance for immunological studies in type 1 diabetes

Diabetes mellitus type 1 is a chronic disease in which the insulin-secreting ss-cells are selectively destroyed by an immune-mediated process. Autoantibodies directed against several islet antigens are useful parameters to estimate the risk to develop diabetes, but cell-mediated immunity involving T lymphocytes plays a major part in causing the specific destruction of ss-cells. T cells are characterized by their antigen-specificity, phenotype and cytokine-secreting profile. T cells that secrete cytokines of the T helper 1 (Th1) type have been shown to transfer diabetes in animal studies, in contrast to T helper 2 (Th2) cytokine-secreting T cells that are thought to be rather nondestructive. In the absence of phenotypic markers for Th1 and Th2 cells, several different approaches have been taken to examine T cell responses in detail. Methods involve T-cell proliferation assays, Enzyme-Linked-Immuno-Sorbent-Assay (ELISA) analysis of secreted cytokines and phenotype analysis applying flow cytometry. A more recent development is ELISPOT analysis, which enables the investigator to determine the qualitative and quantitative antigen-specific immune response on a single-cell level with regard to cytokine secretion. This article aims to give an introduction to the advantages and limitations inherent in the different techniques and their potential relevance for immunological studies in diabetes mellitus type 1.     

GB virus type C infection polarizes T-cell cytokine gene expression toward a Th1 cytokine profile via NS5A protein expression

Human immunodeficiency virus (HIV) disease progression is associated with a helper T cell 1 (Th1) to helper T cell 2 (Th2) cytokine profile switch. Persistent GB virus type C (GBV-C) infection is associated with survival and a serum Th1 cytokine profile in HIV-infected individuals. We found that GBV-C infection increased gene expression of Th1 cytokines and decreased Th2 cytokine expression in peripheral blood mononuclear cells. Furthermore, expression of GBV-C NS5A protein in a CD4(+) cell line resulted in upregulation of Th1 cytokines (tumor necrosis factor α) and downregulation of Th2 cytokines (interleukin 4, interleukin 5, interleukin 10, interleukin 13). GBV-C-induced modulation in T-cell cytokines may contribute to the beneficial effect of GBV-C in HIV-infected individuals.     

急性冠状动脉综合征患者外周血中辅助性T细胞亚群失衡促进血管内皮细胞的损伤作用

目的 分析急性冠状动脉综合征(ACS)和稳定性心绞痛(SAP)患者外周血中1型辅助性T细胞2型辅助性T细胞(Th1/Th2)的变化,探讨Th细胞在ACS中的变化及对血管内皮细胞损伤的作用.方法 收集40例ACS患者和18例SAP患者的外周血,检测外周血中Th1/Th2相关细胞因子的浓度,及不同细胞哑群对人脐静脉内皮细胞(HUVEC)的杀伤作用.结果 ACS组外周血中干扰素-γ(IFN-γ)和白细胞介素-2(IL-2)的浓度,均高于SAP组[IFN-γ:(131.2±42.2)ng/L比(47.6±20.2)ng/L,P<0.05;IL-2:(83.7±21.3)ns/L比(46.2 ±16.7)ng/L,P<0.05],ACS组外周血中IL-10浓度低于SAP组[(16.7±4.3)ng/L比(27.5±5.5)ns/L,P<0.05];ACS组患者的外周血单个核细胞(PBMC)对HUVEC的杀伤作用较SAP组明显增强(PBMC:28.84%±4.20%比20.28%±2.71%,P<0.05),而ACS组患者清除CD4+T细胞的PBMC[(CD4-)-PBMC]对HUVEC的杀伤作用与SAP组比较,差异无统计学意义[(CD4-)-PBMC:20.70%±3.26%比20.28%±2.71%,P>0.05].结论 ACS患者Th1亚群相关细胞凶子水平明显高于SAP患者,Th2亚群相父细胞因子水平显著低于SAP患者,Th1/Th2亚群失衡在PBMC对血管内皮的损伤中起促进作用,提示Th1/Th2亚群失衡可能参与了ACS的发生.     

Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns

Current thinking attributes the balance between T helper 1 (Th1) and Th2 cytokine response patterns in immune responses to the nature of the antigen, the genetic composition of the host, and the cytokines involved in the early interaction between T cells and antigen-presenting cells. Here we introduce glutathione, a tripeptide that regulates intracellular redox and other aspects of cell physiology, as a key regulatory element in this process. By using three different methods to deplete glutathione from T cell receptor transgenic and conventional mice and studying in vivo and/or in vitro responses to three distinct antigens, we show that glutathione levels in antigen-presenting cells determine whether Th1 or Th2 response patterns predominate. These findings present new insights into immune response alterations in HIV and other diseases. Further, they potentially offer an explanation for the well known differences in immune responses in “Th1” and “Th2” mouse strains.     

Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells

Ulcerative colitis (UC) is a chronic relapsed intestinal disease with an increasing incidence around the world. The pathophysiology of UC remains unclear. However, the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research hotspot. Vasoactive intestinal peptide (VIP) is a kind of endogenous neuropeptide with regulatory activity on intestinal immunity. It has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune system. Regulatory B cells (Bregs) are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune circles. Bregs can regulate immune tolerance by producing interleukin (IL)-10, IL-35, and transforming growth factor-β, suppressing autoimmune diseases or excessive inflammatory responses. The secretion of IL-10 by Bregs induces the development of T helper (Th) 0 and Th2 cells. It also induces Th2 cytokines and inhibits Th1 cytokines, thereby inhibiting Th1 cells and the Th1/Th2 balance. With further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients, we believe that Bregs can provide a novel strategy for the clinical treatment of UC. Thus, we aim to review the current literature on this evolving topic.