树突状细胞抗肿瘤疫苗的基础及临床研究现状

树突状细胞（Dendritic Cells,DCs）是目前发现的免疫系统中功能最强的专职递呈细胞。大量研究表明DCs疫苗在抗肿瘤免疫性中扮演着非常重要的角色。本文就DC的生物学特性及功能？在临床肿瘤治疗中的意义？国内外应用DC治疗常见肿瘤的现状进行综述。这将为有关DC的基础和临床试验提供有价值的信息。     

树突状细胞在抗结核分枝杆菌感染中的作用

树突状细胞（Dendritic cells,DCs）是最有效的抗原呈递细胞.DCs能够摄取外来物质,包括结核分枝杆菌（Mycobacterium tuberculosis,MTB）,并将其呈递给效应性淋巴细胞,激发宿主对抗病原微生物感染的免疫反应.因此,树突状细胞与结核分枝杆菌的相互作用在感染初期机体发动免疫应答中十分重要.研究树突状细胞和结核分枝杆菌间的相互作用,有利于从根本上了解细菌-宿主作用机理,为阐明结核分枝杆菌逃避免疫的机制提供依据.     

细胞流变学：一个充满活力的研究领域

细胞流变学：一个充满活力的研究领域Ｃｙｔｏｒｈｅｏｌｏｇｙ龙勉（重庆大学，重庆６３００４４）细胞流变学是研究细胞流动、变形及其他物理学行为的一厂ｌ学科，它是从宏观生物流变学发展起来的，是生物流变学向微观深化过程中在细胞层次上的具体展现。其主要意义在于...     

树突细胞免疫应答结核分枝杆菌基因调控网络的构建与分析

目的 探讨结核分枝杆菌感染树突细胞(dendritic cells,DCs)后宿主DCs基因表达谱的变化,并构建免疫应答基因调控网络,筛选出特征基因模块.方法 通过NCBI GEO datasets数据库,收集结核分枝杆菌感染DCs的芯片表达谱数据,运用R语言分析筛选出差异表达的基因,并对差异表达特征进行统计学分析;基于筛选出的差异基因,整合转录调控元件(TRED)数据库,构建结核分枝杆菌感染DCs中的免疫应答基因调控网络,并筛选出显著功能模块,通过注释及可视化整合分析工具(DAVID)整合KEGG数据库对网络基因进行功能分析(GO analysis)、信号通路分析(Pathway analysis)及疾病相关性分析;对网络基因进一步行蛋白相互作用(PPI)网络分析,并挖掘出关键子网络,筛选高节点度基因;结合基因调控网络中显著功能模块与PPI关键子网络,筛选出结核分枝杆菌感染DCs中的特征基因,并进行ROC曲线分析.结果 构建了DCs免疫应答结核分枝杆菌过程中异常表达的基因调控网络,并提取了包括CREB1、IL6、CEBPA和CCND14个差异表达基因在内的显著功能模块,网络中差异基因与保护性免疫过程或信号通路相关性较大,且在结核通路中有显著功能模块基因CREB1与IL6的分布.PPI网络分析基因调控其节点度Degree最显著的基因为IL6,且在显著功能与通路(inflammatory response与TNF signaling pathway)上均有IL6的分布信息.通过ROC曲线分析CREB1和IL6与DCs免疫应答结核分枝杆菌临床病理特征相关性,其ROC曲线下面积(AUC)分别为0.9114和0.9636.结论 筛选出CREB1与IL6不仅有预测调控关系,且DCs免疫应答结核分枝杆菌的特征基因集特异性强、灵敏度高,可作为表征DCs免疫应答结核分枝杆菌过程的候选标志物,可能成为先天免疫应答向适应性免疫应答的过渡信号.     

树突状细胞瘤苗抗肿瘤功能的研究进展

树突状细胞(DC)是目前已知功能最强的专职抗原提呈细胞,DC在机体免疫应答中的作用尤其是其与肿瘤免疫激活、免疫耐受及相关治疗性疫苗的研究正受到高度关注,文章就DC瘤苗的实验与临床研究进展作一论述.     

免疫RNA体外翻译抗体的研究

从1960年以来,特别是近十年来,国内外对免疫RNA(iRNA)转输特异免疫功能的研究进行了大量的工作,不仅从理论上研究了iRNA转输免疫功能的特性,iRNA的细胞来源,iRNA合成的动力学,iRNA分子性质以及作用机制,而且已开始应用iRNA于肿瘤和肝炎的治疗,并看到了可喜的苗头。近来Paque等人进一步证明iRNA中起     

中枢记忆性T细胞和效应记忆性T细胞

免疫记忆是适应性免疫应答的重要特征,其细胞学基础的阐明是疫苗开发和疾病预防的关键。近年来的研究表明,记忆性T细胞可以被进一步划分为中枢记忆性T细胞和外周记忆性T细胞2个亚群,它们的分布和功能迥异,在生物学特性上也不尽相同。二者关系的深入探讨对于免疫记忆的认识和疾病防治均具有重大的理论和实践意义。     

肿瘤相关巨噬细胞在肿瘤中的研究进展

肿瘤的发生与发展是一个多因素、多步骤的复杂过程.肿瘤的侵袭转移与其所处的肿瘤微环境密切相关,肿瘤微环境由肿瘤细胞本身及其周围的基质细胞、组织液、细胞因子等共同组成,其中基质细胞包括成纤维细胞、各种免疫细胞、内皮细胞、周细胞、血小板、巨噬细胞等.在所有肿瘤炎性细胞中,巨噬细胞约占50%,这些细胞被称为肿瘤相关巨噬细胞,其具有促进肿瘤生长、血管生成、侵袭转移和免疫逃逸等功能,在调节肿瘤进展的各个关键步骤中发挥了重要的作用.本研究就肿瘤相关巨噬细胞的产生、分布及其在肿瘤中的作用进行了综述.     

树突状细胞与妇科肿瘤的免疫治疗

树突状细胞(DC)是目前所知机体内功能最强的专职抗原提呈细胞,可在体内外向T细胞提呈抗原并诱发CTL反应,在抗肿瘤免疫中发挥重要作用.近年采用DC疫苗进行抗肿瘤治疗已成为当今肿瘤生物治疗领域备受关注的焦点之一.针对DC抗肿瘤机制、妇科肿瘤的免疫逃逸及在妇科肿瘤上的应用进行了研究.     

树突状细胞与肿瘤免疫及其在肿瘤免疫治疗方面的应用

DC是功能最强的专职抗原呈递细胞，其首要的功能是诱导机体产生初次免疫应答。近年来由于在细胞活化中共刺激机制的阐明，免疫细胞与肿瘤细胞之间的信号转导及抗原呈递过程研究的深入，使得DC在肿瘤的生物治疗方面的研究取得了较大的进展。本综述了DC与肿瘤预后的关系，DC抗肿瘤机制。DC疫苗的分类以及DC疫苗的临床试验等方面。     

哮喘小鼠骨髓DC细胞因子mRNA的分析

通过体外诱导和扩增小鼠骨髓来源的树突状细胞(DC),研究其中的细胞因子mRNA表达,探讨DC在哮喘中可能的作用机制.为此,利用rmGM-CSF和rmIL-4体外诱导骨髓细胞分化为DC,采用多探针模板的核酸酶保护分析检测骨髓来源的DC中细胞因子mRNA的转录.结果表明,在两种细胞因子的作用下,从骨髓中可以诱导出大量的DC;核酸酶保护分析显示骨髓来源的DC中有IL-13,IL-9和IL-3mRNA的转录,并且哮喘组表达IL-13mRNA和IL-9mRNA的相对水平与对照组相比有明显的差异性,P<0.05;而IL-3mRNA的表达在两组鼠中的表达水平没有差异性,P>0.05.可以认为DC在哮喘的形成和发展中起重要作用,提示了靶向于DC的治疗可能成为哮喘治疗的新目标.     

T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases

Primary T-cell responses in lymph nodes (LNs) require contact-dependent information exchange between T cells and dendritic cells (DCs). Because lymphocytes continually enter and leave normal LNs, the resident lymphocyte pool is composed of non-synchronized cells with different dwell times that display heterogeneous behaviour in mouse LNs in vitro. Here we employ two-photon microscopy in vivo to study antigen-presenting DCs and naive T cells whose dwell time in LNs was synchronized. During the first 8 h after entering from the blood, T cells underwent multiple short encounters with DCs, progressively decreased their motility, and upregulated activation markers. During the subsequent 12 h T cells formed long-lasting stable conjugates with DCs and began to secrete interleukin-2 and interferon-gamma. On the second day, coinciding with the onset of proliferation, T cells resumed their rapid migration and short DC contacts. Thus, T-cell priming by DCs occurs in three successive stages: transient serial encounters during the first activation phase are followed by a second phase of stable contacts culminating in cytokine production, which makes a transition into a third phase of high motility and rapid proliferation.     

Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules

While patrolling the body in search of foreign antigens, naive lymphocytes continuously circulate from the blood, through the lymph nodes, into the lymphatic vessels and back to the blood. This process, called lymphocyte recirculation, provides the body with effective immune surveillance for foreign invaders and for alterations to the body's own cells. However, the mechanisms that regulate lymphocyte recirculation during homeostasis remain incompletely characterized. Here we show that dendritic cells (DCs), which are well known for their role in antigen presentation to T lymphocytes, control the entry of naive lymphocytes to lymph nodes by modulating the phenotype of high endothelial venules (HEVs), which are blood vessels specialized in lymphocyte recruitment. We found that in vivo depletion of CD11c(+) DCs in adult mice over a 1-week period induces a reduction in the size and cellularity of the peripheral and mucosal lymph nodes. In the absence of DCs, the mature adult HEV phenotype reverts to an immature neonatal phenotype, and HEV-mediated lymphocyte recruitment to lymph nodes is inhibited. Co-culture experiments showed that the effect of DCs on HEV endothelial cells is direct and requires lymphotoxin-β-receptor-dependent signalling. DCs express lymphotoxin, and DC-derived lymphotoxin is important for lymphocyte homing to lymph nodes in vivo. Together, our results reveal a previously unsuspected role for DCs in the regulation of lymphocyte recirculation during immune surveillance.     

Progress in studies on the characteristics of human amnion mesenchymal cells

The amniotic membrane (AM) in humans is the innermost fetal membrane and is composed of amnion mesenchymal cells (hAMCs) and amnion epithelial cells (hAECs). The former are derived from the extra-embryonic mesoderm of the primitive streak, and the latter from the fetal ectoderm. Numerous studies have shown that both hAMCs and hAECs display stem cell characteristics. In this review, we examine the progress made in understanding the characteristics of hAMCs, including information on the structure and function of AM and hAMCs, their immunological features, and the pluripotency of hAMCs.     

Direct observation of ligand recognition by T cells

The activation of T cells through interaction of their T-cell receptors with antigenic peptide bound to major histocompatibility complex (MHC) on the surface of antigen presenting cells (APCs) is a crucial step in adaptive immunity. Here we use three-dimensional fluorescence microscopy to visualize individual peptide-I-E(k) class II MHC complexes labelled with the phycobiliprotein phycoerythrin in an effort to characterize T-cell sensitivity and the requirements for forming an immunological synapse in single cells. We show that T cells expressing the CD4 antigen respond with transient calcium signalling to even a single agonist peptide-MHC ligand, and that the organization of molecules in the contact zone of the T cell and APC takes on the characteristics of an immunological synapse when only about ten agonists are present. This sensitivity is highly dependent on CD4, because blocking this molecule with antibodies renders T cells unable to detect less than about 30 ligands.     

体外诱导骨肉瘤特异性抗肿瘤的免疫实验

采用分离骨肉瘤患者外周血单核细胞体外诱导DC细胞,Trizol法提取患者骨肉瘤细胞总RNA,用总RNA转染DC并诱导特异性CTL的扩增,用MTT法检测淋巴细胞的增殖和CTL的杀伤活性。探讨骨肉瘤细胞总RNA转染的DC疫苗体外诱导特异性抗肿瘤免疫的能力。经骨肉瘤细胞总RNA转染的DC特异性表面标志及功能相关分子表达均上调,转染后的DC可显著刺激自体T淋巴细胞增殖,诱导的特异性CTL对靶细胞的杀伤率显著高于单纯淋巴细胞和未经转染的DC。说明骨肉瘤细胞总RNA转染的DC疫苗可在体外诱导出特异性抗肿瘤免疫。     

Structural characteristics and biological functions of the HIV-1 gp120 V3 region

Recent studies demonstrate that the V3 loop of HIV-1 gp120 plays an important role in the attachment of HIV-1 to the target cells. Several amino acids in this domain are involved in the interaction of gp120 with the co-receptors. The V3 loop elicits one of the earliest antiviral antibody responses in HIV-1 infection and has been identified as the principal neutralizing determinant (PND). A subset of antibodies to V3 loop show a broad range of neutralizing activity. Unfortunately, this loop undergoes broad mutation and is one of the hypervariable regions. Mutations of some amino acids in this PND could affect syncytium formation, virus infectivity and neutralization. Knowing the structural characteristics and biological functions of the V3 region could help us to understand mechanism of HIV infection and to develop new strategy against HIV-1. In this review, the structural characteristics, variation and biological functions of the V3 loop as well as immunological responses to the V3 loop are discussed.     

Taking dendritic cells into medicine

Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.