调节性T细胞在乙型、丙型、戊型肝炎中的作用

调节性T细胞是T淋巴细胞中一群具有主动免疫抑制作用的特殊亚群,可抑制免疫效应过度活化、维持机体免疫稳态.调节性T细胞数量的变化与自身免疫疾病、感染性疾病、肿瘤疾病和移植排斥反应的发生密切相关.本文对近年国内外关于调节性T细胞在病毒性肝炎(乙型肝炎、丙型肝炎、戊型肝炎)中作用的相关研究进行综述.     

T细胞免疫调节机制在心力衰竭心肌纤维化中的作用

心肌重构在心力衰竭(心衰)的发生及发展中起着至关重要的作用,当心脏急性或慢性损伤时,多种细胞机制参与了心肌的重构过程,这其中免疫细胞如T淋巴细胞可以通过细胞信号相关蛋白,激活心肌成纤维细胞,导致前胶原在细胞外基质沉积促使心肌纤维化的形成。了解T细胞亚群与成纤维细胞在免疫炎症机制介导心肌纤维化中的作用,有助于从免疫炎症角度进一步了解心肌重构,为心力衰竭的预后及治疗提供新的思路。     

肺癌与T淋巴细胞亚群相关性研究

肺癌是目前全世界最常见的恶性肿瘤,发病率和病死率居于恶性肿瘤的首位[1]。肺癌的发生、发展与机体免疫状态有关,机体的免疫状态特别是T淋巴细胞介导的细胞免疫反应起重要作用,T淋巴细胞亚群能维持机体的正常免疫平衡,在杀伤肿瘤细胞、控制肿瘤生长中起重要作用,当外周T淋巴细胞亚群在数量和功能发生异常时,机体免疫功能就可能出现紊乱,进而可促进肿瘤的发生、发展。现就肺癌与外周血T淋巴细胞亚群变化的相关研究做一综述。     

胃癌与T淋巴细胞亚群关系的研究进展

胃癌是我国最常见的恶性肿瘤之一.胃癌的发生、发展与机体免疫状态有密切的关系.T淋巴细胞不仅是人体细胞免疫的主要效应细胞,而且是重要的免疫调节细胞,维持机体正常免疫功能,在杀伤肿瘤细胞、控制肿瘤生长中起重要作用.当外周T淋巴细胞亚群在数量和功能发生异常时,可导致免疫系统紊乱并发生一系列的病理变化,进而可导致肿瘤的发生、发展.T淋巴细胞亚群在恶性肿瘤发病机制中的作用日益受到人们重视.本文就胃癌与T淋巴细胞亚群关系的研究进展进行综述.     

心力衰竭患者T淋巴细胞亚群和自然杀伤细胞活性的变化

本研究检测慢性心力衰竭（心衰）患循环T淋巴细胞亚群和自然杀伤（NK）细胞活性，探讨心衰免疫功能异常的某些机制。     

登革病毒感染者外周血T淋巴细胞亚群数量的变化及其临床意义

目的观察登革热患者外周血T淋巴细胞亚群数量变化的特点并探讨其临床意义。方法用流式细胞仪检测不同发病时间71例登革热患者外周血中总T淋巴细胞(CD3+)、CD4+T淋巴细胞和CD8+T淋巴细胞的数量,并将急性期患者、恢复期患者及正常人T淋巴细胞及其亚群数量进行比较,组间数据比较采用t检验。结果与正常对照组相比,急性期登革热患者T细胞和CD4+T细胞都显著减少(P<0.01)、CD4+T/CD8+T比值显著降低(P<0.01),恢复期登革热患者上述指标没有显著性差异(P>0.05);与急性期相比,恢复期登革热患者CD4+T细胞显著升高(P<0.01);急性期、恢复期登革热患者和正常对照组CD8+T细胞数量没有显著性差异(P>0.05)。登革热患者T淋巴细胞亚群数量和CD4+T/CD8+T比值随着发病时间的增加而逐渐上升。结论登革热患者急性期细胞免疫异常,通过治疗可以逐渐恢复。T淋巴细胞亚群的检测可作为监测登革热患者免疫功能的一个指标,对于病人的治疗和预后有一定的意义。细胞免疫异常可能在登革热的发病中起重要作用。     

赤栀黄合剂对中毒性肝炎小鼠淋巴细胞毒和T细胞亚群的影响

用四氯化碳(CCl_4)造成14只小鼠中毒性肝炎模型,采用淋巴细胞毒实验和间接免疫荧光试验,观察赤栀黄合剂对7只小鼠中毒性肝炎模型胸腺细胞毒及T细胞亚群的影响。该合剂可增强小鼠胸腺细胞的细胞毒作用(P<0.01),使T细胞及T细胞亚群细胞数量显著下降(P<0.01)。表明赤栀黄合剂能调节中毒性肝炎小鼠的免疫功能。     

老年SD大鼠脾脏和外周血T淋巴细胞亚群的变化

目的探讨SD老年大鼠脾脏和外周血T淋巴细胞亚群的变化。方法流式细胞仪检测老年大鼠(10只)和青年鼠(5只)脾脏和血液T淋巴细胞亚群的变化。结果 SD老年大鼠脾脏和外周血T淋巴细胞亚群阳性率的变化相一致,CD3+、CD4+、CD8+细胞阳性率均低于青年组水平,且CD4细胞阳性率均明显低于青年组(P<0.05);CD4+/CD8+比值均低于青年组,在脾脏CD4+/CD8+比值与青年组相比具有显著性差异(P<0.05)。结论 SD老年大鼠脾脏和外周血T胞亚群阳性率均减少,且CD4+/CD8+比值明显降低,提示SD老年大鼠免疫功能的衰退和紊乱与T细胞密切相关。     

慢性乙型肝炎患者外周血CD8~+T淋巴细胞亚群T淋巴细胞受体β链互补决定区3谱型研究

目的 研究慢性乙型肝炎(CHB)患者外周血CD8+T淋巴细胞亚群T淋巴细胞受体(TCR)β链Ⅴ区(BV)中互补决定区3(CDR3)谱型特点.方法 采集8例CHB患者(ALT>2倍正常值上限)的抗凝血,分离外周血单个核细胞,磁珠分选CD8~+T淋巴细胞亚群,提取RNA并应用逆转录-聚合酶链反应扩增TCR BV中CDR3基因的24个家族,采用免疫指纹技术进行TCRBV各家族基因扫描和谱型分析.不同细胞亚群间数据比较采用配对t检验.结果 8例患者外周血淋巴细胞TCR BV家族CDR3谱型发生明显偏移,表现为单克隆性,寡克隆性及偏峰性克隆增生.8例患者CD8~+T淋巴细胞亚群发生TCR BV CDR3谱型偏移家族总个数高于去除CD8~+T淋巴细胞群的外周血单个核细胞[(10.6±4.7)个比(4.1±3.1)个,t=6.619,P<0.01)];比较单、寡克隆增生2种形式偏移的家族,CD8+T淋巴细胞亚群也高于代表CD4+T淋巴细胞的去除CD8~+T淋巴细胞群的外周血单个核细胞[(8.8±4.5)个比(3.9±2.8)个,t=5.706,P<0.01].对其中3例患者磁珠分选前后TCR BV谱型的比较发现,分选后CD8+T淋巴细胞亚群发生TCR BV谱型偏移家族数均高于分选前.结论 通过淋巴细胞亚群分选方式分析TCR BV家族CDR3谱型变化可以减少不同淋巴细胞亚群之间的峰型重叠干扰;应用这一方法分析外周血CD8~+T淋巴细胞亚群克隆增生程度有助于了解CHB患者炎症的发生机制.     

T淋巴细胞亚群及其细胞因子在心房颤动发病机制中作用的研究进展

心房颤动的研究一直是心律失常的重点。近年研究发现,免疫细胞群参与房颤的发生发展。T淋巴细胞及其亚群是机体免疫中的重要因子,主要分为辅助性T细胞(Th细胞)、调节性T细胞(Tregs细胞)和抑制性T细胞(Ts细胞),均参与了房颤的发生、进展及维持。     

MicroRNA Involvement in Immune Activation During Heart Failure

Heart failure is one of the common end stages of cardiovascular diseases, the leading cause of death in developed countries. Molecular mechanisms underlying the development of heart failure remain elusive but there is a consistent observation of chronic immune activation and aberrant microRNA (miRNA) expression that is present in failing hearts. This review will focus on the interplay between the immune system and miRNAs as factors that play a role during the development of heart failure. Several studies have shown that heart failure patients can be characterized by a sustained innate immune activation. The role of inflammatory signaling is discussed and TLR4 signaling, IL-1β, TNFα and IL-6 expression appears to coincide with the development of heart failure. Furthermore, we describe the implication of the renin angiotensin aldosteron system in immunity and heart failure. In the past decade microRNAs (miRNAs), small non-coding RNAs that translationally repress protein synthesis by binding to partially complementary sequences of mRNA, have come to light as important regulators of several kinds of cardiovascular diseases including cardiac hypertrophy and heart failure. The involvement of differentially expressed miRNAs in the inflammation that occurs during the development of heart failure is still subject of investigation. Here, we summarize and comment on the first studies in this field and hypothesize on the putative involvement of certain miRNAs in heart failure. MicroRNAs have been shown to be critical regulators of cardiac function and inflammation. Future research will have to point out if dampening the immune response, and the miRNAs associated with it, during the development of heart failure is a therapeutically plausible route to follow.     

Non-cardiomyocyte microRNAs in heart failure

Multiple structural changes are known to occur in a failing heart. Myocyte hypertrophy, cardiomyocyte apoptosis, interstitial fibrosis, reduced capillary density, and activation of the immune system are all involved in the pathogenesis and progression of heart failure (HF). The molecular mechanisms underlying these changes of the myocardium have been extensively studied, and many pathways involved in these processes have been uncovered. Recently, it has become evident that a novel class of small non-coding RNAs, called miRNAs, also plays a key role in these structural changes of the heart. This review summarizes the current insights on the role of miRNAs outside myocytes in the heart. Specifically, we will discuss miRNA function in fibroblasts, endothelial cells and immune cells in response to myocardial stress as occurs after myocardial infarction and in the pathogenesis of HF.     

巨噬细胞与间充质干细胞相互作用及其对缺血性心脏病的影响

心肌梗死发生后,缺血及周边区域发生的炎症反应贯穿了心肌组织修复及纤维化的始终。巨噬细胞作为炎症反应的重要组分,在心肌损伤后的修复过程中至关重要。不同亚型的巨噬细胞参与了心肌梗死的各个阶段,并发挥着吞噬凋亡细胞、促进血管新生、促进瘢痕形成等多种作用。移植间充质干细胞也因具有免疫调控、旁分泌心肌保护等多种效应,被广泛用于缺血性心衰的研究中。近年来研究发现,巨噬细胞和间充质干细胞在治疗缺血性心脏病中有着密切联系,间充质干细胞可减少促炎型巨噬细胞在炎症部位的募集,并诱导巨噬细胞由促炎型向抗炎型转化,从而促进心肌修复。而巨噬细胞可影响间充质干细胞的生存、增殖、迁移及免疫调控等功能,从而改变其心肌修复效果。本文就巨噬细胞与间充质干细胞相互影响及其在缺血性心脏病中的作用与应用前景进行综述。     

Impaired up-regulation of CD25 on CD4+ T cells in IFN-gamma knockout mice is associated with progression of myocarditis to heart failure

Inflammation has been recognized increasingly as a critical pathologic component of a number of heart diseases. A mouse model of autoimmune myocarditis was developed to study the role of immune mediators in the development of cardiac dysfunction. We have found previously that IFN-gamma deficiency promotes inflammation in murine myocarditis. It has been unclear, however, how IFN-gamma deficiency in myocarditis affects cardiac function and what underlying immune mechanisms are responsible for these effects. In this work, we show that IFN-gamma knockout (KO) mice have more pronounced systolic and diastolic dysfunction and greater frequency of progression to dilated cardiomyopathy and heart failure compared with WT mice. Cardiac dysfunction in the KO mice is associated with the expansion of activated (CD44(high)) CD3+ T cells due to reduced apoptosis of CD4+, but not CD8+, T cells. CD4+ T cells in the KO mice show impaired up-regulation of CD25 upon activation, resulting in the expansion of CD4+CD44+CD25- T cells and their infiltration into the heart. CD4+CD25- T cells are less apoptosis-prone compared with the CD25+ population, and their infiltration into the heart is associated with greater severity of myocarditis. We conclude that IFN-gamma deficiency in autoimmune myocarditis is associated with preferential expansion of CD4+CD44+CD25- T cells resulting in increased cardiac inflammation. An exaggerated inflammatory response in IFN-gamma KO mice causes cardiac dysfunction, leading to dilated cardiomyopathy and heart failure.     

系统性红斑狼疮合并心力衰竭的发病机制及病因

系统性红斑狼疮患者合并心力衰竭较普通人群常见,在不同年龄、性别和种族之间的发病风险存在较大差异。炎症和免疫反应可能是系统性红斑狼疮合并心力衰竭的主要发病机制。冠心病、高血压、糖尿病和瓣膜性心脏病是其发病的重要原因。     

Subclinical Inflammation in Heart Failure: A Neutrophil Perspective

Although it is widely recognized that inflammation plays a critical role in the development and pathology of heart failure (HF), very little is known about the involvement of one of the most abundant immune cells in the blood, a primary immune response cell: the neutrophil. This review summarizes the current literature on the role of subclinical inflammation, with a focus on the neutrophil in the pathophysiology of the HF syndrome. Some emerging therapeutic strategies are also discussed.     

组胺与固有免疫调控及其在心血管疾病中的作用

组胺是人体内重要的参与免疫调节和过敏反应、神经信号传递、胃酸分泌、造血细胞生成等生理病理过程的小分子生物胺。组胺通过作用于细胞表面的组胺受体,激活相应的胞内信号通路,进而发挥一系列生理效应。已有研究表明,炎症与免疫反应贯穿冠心病、心力衰竭、心肌心包炎等心血管疾病的发生发展过程,其中组胺的作用颇受关注。本综述将着眼于探讨组胺对固有免疫反应的调控作用及其对心血管疾病的影响。     

Could interferon-gamma be a therapeutic target for treating heart failure?

The cytokine interferon-gamma (IFN-γ) is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. While a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will (1) discuss the source of IFN-γ in the diseased heart; (2) summarize the data from animal studies; (3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; (4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and (5) present the clinical evidence supporting a role for IFN-γ in heart failure.     

High-density lipoprotein-mediated cardioprotection in heart failure

The prevalence of heart failure (HF), including reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), has increased significantly worldwide. However, the prognosis and treatment of HF are still not good. Recent studies have demonstrated that high-density lipoprotein (HDL) plays an important role in cardiac repair during HF. The exact role and mechanism of HDL in the regulation of HF remain unexplained. Here, we discuss recent findings regarding HDL in the progression of HF, such as the regulation of excitation-contraction coupling, energy homeostasis, inflammation, neurohormone activation, and microvascular dysfunction. The effects of HDL on the regulation of cardiac-related cells, such as endothelial cells (ECs), cardiomyocytes (CMs), and on cardiac resident immune cell dysfunction in HF are also explained. An in-depth understanding of HDL function in the heart may provide new strategies for the prevention and treatment of HF.

     

High fat diet downregulates regulatory T cells in the myocardium of spontaneous hypertensive rats

Background and aimRegulatory T cells (Tregs) play an important role in cardiovascular complications with the immune response. However, the role of Tregs in high fat diet (HFD)-induced myocardial fibrosis has not been fully elucidated to date. Therefore, we investigated whether HFD suppresses Tregs activation in the myocardium of spontaneously hypertensive rats (SHRs), which aggregates myocardial fibrosis.Methods and resultsEight-week-old male SHRs were fed to either HFD or control diet (CHO) groups for 12 weeks. We measured Tregs (CD4+FoxP3+) in the heart and mediastinal lymph nodes (LNs). The flow cytometry analysis confirmed that SHR-HFD exhibited a decreased Tregs compared to that of SHR-CHO in the heart and mediastinal LNs. Furthermore, the CD4 and FoxP3 antigens were used in the immunofluorescence microscopy of Tregs in the heart tissues. In the heart, dual staining for the Treg population was increased more in SHR-CHO than it was in SHR-HFD rats. In line with these findings, SHR-HFD significantly exacerbated myocardial fibrosis.ConclusionWe found that diet-induced obesity typically showed an exacerbated myocardial fibrosis and down-regulation of Tregs pathway in the heart and mediastinal LNs. Therefore, we suggest that the up-regulation of Tregs may be a promising therapeutic approach to preventing obesity induced heart failure.