类风湿关节炎外周血树突状细胞亚群的分析

类风湿关节炎（RA）是目前最为常见的自身免疫性疾病之一．其发生和发展是由多种诱发因素和机体免疫异常所造成的,其中抗原提呈功能的异常是一个重要方面。树突状细胞（DC）是目前所知的机体内功能最强的抗原提呈细胞（APC）,它不仅是机体免疫应答的始动者,而且在诱导免疫耐受、调节T细胞介导的免疫应答方面都发挥着重要的作用。目前国内有关DC与RA发病关系的研究少见报道,研究采用流式细胞分析技术,通过组合性DC表面标志的测定,观察RA患者外周血DC表型表达状况、DC亚群水平变化及其与RA活动指标和活动度的关系,探讨DC在RA发病中的作用。     

肝树突状细胞与HCV感染

树突状细胞(dendritic cell，DC)是一类专职抗原提呈细胞(APC)，虽在机体内的数量较少，但分布于机体全身，是启动机体初次免疫应答功能最强的APC。DC能通过MHC-Ⅰ、Ⅱ类途径提呈所遇到的任何抗原，并通过删肽复合物，共刺激分子(B7、CD40)以及DC-CKl等趋化因子趋化、转化、激活静息T细胞，从而激发初次免疫反应，有效控制机体免疫应答的过程。目前有证据显示DC与多种病毒(HBV、HCV、HIV和HCMV等)的发病机理和机体抗病毒免疫的作用机制相关。HCV感染后易造成体内持续感染，其发生机制十分复杂，而机体内DC的功能、分化和成熟均影响HCV在体内的存在，现将肝脏DC的特点，HCV对DC影响及其作用机制作一综述。     

树突状细胞在抗HIV-1感染免疫预防与治疗中的应用

树突状细胞（DC）不仅是已知惟一能够激活初始T淋巴细胞的抗原提呈细胞，而且也是已知最强的抗原提呈细胞（APC），其对抗原的提呈能力远大于巨噬细胞。经抗原刺激的DC回输到体内后，能够迁移到淋巴结，释放多种细胞因子，同时激活T淋巴细胞的分化和分裂，产生抗原特异性的细胞毒性T淋巴细胞（CTL），这些细胞因子和特异性CTL能够有效地促进或直接杀伤表达该抗原的细胞。基于这个原理，利用HIV-1抗原刺激DC所诱导的免疫对HIV-1感染进行免疫预防和治疗的研究已取得初步进展；将高效抗逆转录病毒疗法（highly active antiretroviral therapy，HARRT）和DC免疫治疗相结合的方案也已成为治疗AIDS的较好方法之一。本文中将对近年来DC在抗HIV-1感染免疫预防与免疫治疗中的应用研究进展作一综述。     

树突状细胞与细菌、原虫感染免疫研究进展

树突状细胞 (DC)是功能最强大的专职抗原提呈细胞 ,虽然DC与某些细菌、原虫的相互作用过程中可促使病原体增殖、播散和机体免疫抑制 ,但在大多数病原体的感染中可以有效地摄取、提呈抗原 ,诱导机体对病原体的特异性保护免疫。以DC为基础的主动性抗感染免疫治疗对于有DC数量和 /或功能缺陷的细菌、原虫感染具有重要价值     

肝树突状细胞与HCV感染

树突状细胞(dendritic cell,DC)是一类专职抗原提呈细胞(APC),虽在机体内的数量较少,但分布于机体全身,是启动机体初次免疫应答功能最强的APC[1].DC能通过MHC-I、Ⅱ类途径提呈所遇到的任何抗原,并通过MHC/肽复合物,共刺激分子(B7、CD40)以及DC-CK1等趋化因子趋化、转化、激活静息T细胞,从而激发初次免疫反应,有效控制机体免疫应答的过程.目前有证据显示DC与多种病毒(HBV、HCV、HIV和HCMV等)的发病机理和机体抗病毒免疫的作用机制相关.HCV感染后易造成体内持续感染,其发生机制十分复杂,而机体内DC的功能、分化和成熟均影响HCV在体内的存在,现将肝脏IC的特点,HCV对DC影响及其作用机制作一综述.     

树突状细胞与细菌、原虫感染免疫研究进展

树突状细胞(DC)是功能最强大的专职抗原提呈细胞，虽然DC与某些细菌、原虫的相互作用过程中可促使病原体增殖、播散和机体免疫抑制，但在大多数病原体的感染中可以有效地摄取、提呈抗原，诱导机体对病原体的特异性保护免疫。以DC为基础的主动性抗感染免疫治疗对于有DC数量和，或功能缺陷的细菌、原虫感染具有重要价值。     

树突状细胞与抗肿瘤免疫

树突状细胞（dendritic cell，DC）因其胞膜向外伸出许多星状突起类似于神经细胞的树突，因而得名。DC首先由Steinman和Cohn于1973年从小鼠脾脏中分离出，是与巨噬细胞、粒细胞和淋巴细胞等白细胞形态、功能相异的重要免疫辅佐细胞。DC是免疫应答中重要的免疫细胞，是目前所知功能最强的一种专职抗原提呈细胞（antigen presenting cells，APC），也是体内唯一能激活初始型T细胞的抗原提呈细胞。对于维持正常机体免疫系统的自身稳态，DC起着重要作用。同时，作为机体免疫的始动者，DC在抗病毒、抗肿瘤免疫反应及免疫缺陷方面，发挥着十分重要的作用。近年来，随着肿瘤免疫学和分子生物学的快速发展，人们对DC的认识不断深入，DC已成为生物医学界研究抗肿瘤免疫的热点之一。因此，本文就与抗肿瘤免疫相关的DC研究做一简要综述。     

Toll样受体8激动剂在树突状细胞抗肿瘤免疫治疗中的研究进展

树突状细胞(DC)作为功能最强大的专职抗原提呈细胞,在诱导机体产生抗原特异性细胞毒性T细胞(CTL)中发挥重要作用。因此,现在的研究聚焦于使用免疫刺激性配体以增强DC在肿瘤中的抗原提呈功能,促进Th1型细胞免疫。由于小分子Toll样受体8(TLR8)激动剂直接激活DC、增强DC抗原提呈功能和细胞免疫应答,特别是Th1细胞应答。因此,TLR8激动剂已经成为抗肿瘤免疫调节药物或免疫佐剂的研究热点。本文在总结TLR8激动剂的结构和免疫调节作用的基础上,重点阐明TLR8激动剂增强DC免疫原性的机制,以及TLR8激动剂用于制备新一代DC疫苗的研究进展,探讨TLR8激动剂作为免疫刺激性配体在肿瘤免疫治疗中的临床应用前景。     

树突状细胞与特异性肿瘤免疫治疗

树突状细胞（DC）是体内功能最强的抗原提呈细胞（APC）,也是抗原特异性免疫应答的始动者,由DC活的T细胞介导的免疫应答在机体抗肿瘤过程中起着主导作用。本主要对DC参与抗肿瘤的机制,DC与肿瘤免疫逃逸的关系及近年来DC在肿瘤生物治疗方面的研究进展作一综述,以DC为基础的肿瘤治疗主要有两种方式：（1）免疫治疗：肿瘤抗原体外冲击致敏DC后回输体内;（2）基因治疗：以目的基因转染DC后回输体内。     

CD40分子在树突状细胞中的信号转导通路

树突状细胞 (DC )作为体内功能最强的抗原提呈细胞 (APC ) ,是启动机体免疫应答的中心环节[1] 。未成熟DC定居在外周组织 ,具有极强的捕获抗原能力 ,通过多种方式捕获入侵的病原体、损伤或恶变的组织后迁移至淋巴结 ,将加工过的抗原以MHC 抗原肽的形式提呈给T细胞启动机体免疫应答。在此过程中 ,DC逐渐发育成熟 ,伴随着膜表面黏附分子表达的变化以及MHCII类分子和共刺激分子如CD4 0、OX4 0L、CD80、CD86表达的上调。然而 ,DC抗原提呈功能的完全成熟需要T细胞提供的共刺激信号 ,其中CD4 0相关的信号通路在此过程中发挥了重要作用     

结核病患者外周血树突状细胞及其亚群的变化

目的:分析不同结核病患者外周血树突状细胞(DCs)及其亚群的变化,并进行免疫机制探讨。方法:就诊于我院2008-11/2009-08的结核病患者32例(实验组),同期在我院进行健康体检者11例(对照组),采用流式细胞术(FCM)检测了结核病患者(包括19例初治患者和13例复治患者,以及痰涂片结果不同的19例肺结核患者)和对照组中外周血中DCs及其亚群的变化。结果:实验组DC1亚群的比率和DCs的总数分别为(0.28±0.13)%和(0.42±0.19)%,明显低于对照组的DC1亚群的比率和DCs的总数(0.47±0.23)%和(0.65±0.22)%(P0.01)。痰涂片阳性患者外周血中DC1亚群的比率和DCs的总数分别为(0.16±0.04)%和(0.24±0.06)%,明显低于痰涂片阴性患者DC1亚群的比率和DCs的总数(0.28±0.14)%和(0.43±0.12)%(P0.05)。初治患者与复治患者外周血中DCs的总数及其亚群的比率无统计学意义(P0.05)。结论:DCs可作为结核病传染源初筛和抗结核疗效观察的参考指标,反映不同结核病患者的免疫状态。     

Induction of high levels of protective immunity in mice after vaccination using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis

Adoptively transferred dendritic cells presenting antigens derived from different pathogens have been shown to elicit specific T cell responses and to induce protective antibacterial immunity. We describe here the induction of high levels of protective immunity in mice using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis. We provide evidence that protection is superior to BCG and that it is associated with increased priming of CD4+ and CD8+ T cells specific for mycobacterial antigens. This method for generating high levels of anti-bacterial protective immunity could be helpful in the design of novel vaccines against tuberculosis and other intracellular pathogens.     

Dendritic cells: inciting and inhibiting autoimmunity

Dendritic cells are considered the most influential antigen presenting cells in the body because of their unique role in initiating immunity against threatening antigens. Recent studies addressing the consequences of self-antigen presentation by dendritic cells revealed the unexpected ability of these antigen presenting cells to inhibit T cell-mediated autoimmune diseases. The specific mechanisms by which dendritic cells suppress immune responses have been explored during the past year. These efforts indicate that extrathymic dendritic cells control autoimmunity by inducing peripheral T cell tolerance, a function intimately linked to their state of maturation.     

Role of chaperones and FcgammaR in immunogenic death

Cell death under physiologic conditions does not lead to the induction of immunity. However recognition of stressed or opsonized cells can trigger immune responses. Recent studies have begun to illustrate the critical role of molecular chaperones such as inducible heat shock proteins in mediating immunogenicity of stressed cells. Immunity to opsonized cells depends in part on the engagement and the balance of activating and inhibitory FcgammaRs on antigen presenting dendritic cells. Understanding both these pathways of immunogenic cell death may yield novel approaches to regulate immunity.     

Dendritic cells efficiently immunoselect mycobacterial-reactive T cells in human blood, including clonable antigen-reactive precursors.

Given the persistence of tuberculosis throughout the world, the delineation of mechanisms that lead to protective immunity to Mycobacterium tuberculosis is important. We have evaluated the presenting function of human dendritic cells for mycobacterial antigens, since these antigen-presenting cells (APC) are particularly effective in initiating antigen-specific T-cell responses. Dendritic cells from blood prove to be active APC for mycobacteria-specific proliferative responses by CD4+ T cells from bacillus Calmette-Guérin (BCG)-vaccinated individuals. In the first 24-48 hr of the response, dendritic cells that have been pulsed with mycobacterial antigens, including live BCG, effectively bind T cells forming discrete cell clusters. The clusters represent about 1% of the applied T cells. Clusters are highly enriched in mycobacterial reactivity while the non-clusters are depleted. Clustered T cells can be used as a starting point to expand antigen-specific cell lines. Mitogen and allogeneic feeder cells were used as APC to expand the mycobacterial-reactive lines, because the antigen-specific T cells had been preselected by virtue of their binding to antigen-pulsed dendritic cells. We discuss the advantages of obtaining antigen-reactive T cells by using dendritic cells as immunoadsorbents. These lines should help delineate the range of mycobacterial antigens and T-cell responses that participate in host responses to mycobacteria.     

Roles of toll-like receptors in natural interferon-producing cells as sensors in immune surveillance

Natural IFN-alpha/beta producing cells (IPCs) play a central role in innate immunity against microbial infections. In primary immune responses, toll-like receptors (TLRs), as major pattern-recognition receptors, are essential for IPCs as well as other antigen presenting cell (APC) subsets to recognize microbes. IPCs unequivocally express TLR7 and TLR9, and can respond to the respective ligand to produce IFN-alpha/beta and to rapidly differentiate into dendritic cells (DCs). Thereby, IPCs can not only activate innate immune system but also provoke T cell responses. Thus, IPCs link innate and adaptive immunity through TLR system. In addition, recent work has revealed the regulatory system of DC subsets in response to microbial invasion. In this context, by the different but complementary expression profile of TLRs, IPCs together with myeloid APC subsets constitute a rational system of immune surveillance that can cover a wide variety of pathogens and enlarge immune adjuvant effects.     

CD1c(+) immature myeloid dendritic cells are predominant in cord blood of healthy neonates

It has been suggested lately that some types of antigen presenting cells-myeloid dendritic (DC-1) cells can differentiate the immune response towards Th1 type immunity, whereas lymphoid cells (DC-2) can stimulate Th2 type immunity. It has been observed that neonates are deficient in Th1 response. The purpose of our study was to estimate the proportions of immature myeloid (CD1c(+)) and lymphoid (BDCA-2(+), BDCA-4(+)) dendritic cells and the CD1c(+):BDCA-2(+) cell ratio in cord blood of healthy neonates in comparison with dendritic cells of healthy adults. Thirty healthy neonates born from normal pregnancies and 30 healthy adults were included in the study. The dendritic cells were isolated from cord and peripheral blood, stained with anti-CD1c, anti-BDCA-2, anti-BDCA-4, anti-CD123 and anti-CD19 monoclonal antibodies and estimated using flow cytometry. The percentage of CD1c(+) dendritic cells in cord blood of healthy newborns did not differ significantly when compared to those in peripheral blood of healthy adults. The percentages of cord blood BDCA-2(+) and BDCA-4(+) dendritic cells of neonates were significantly lower when compared to lymphoid dendritic cells in peripheral blood of adults. The CD1c(+):BDCA-2(+) ratio was significantly higher in cord blood of neonates in comparison with CD1c(+):BDCA-2(+) ratio in adult's blood. Myeloid and lymphoid dendritic cells may be involved in the immune regulation during fetal development. Immature myeloid dendritic cells are predominant in cord blood of healthy neonates. Immature lymphoid dendritic cells are not the major population of dendritic cells in cord blood.     

Reciprocal stimulation of gammadelta T cells and dendritic cells during the anti-mycobacterial immune response

Gammadelta T cells and dendritic cells (DC) are two distinct cell types of innate immunity that participate in early phases of immune response against Mycobacterium tuberculosis infection. Here we show that a close functional relationship exists between these cell populations. Using an in vitro coculture system, Vgamma1 T cells from Tcrb(-/- )mice were found to be activated by DC infected in vitro with BCG, as indicated by the elevated CD69 expression, IFN-gamma secretion and cytotoxic activity. This activation process was due to a non-cognate mechanism since it required neither cell to cell contact nor interaction between the TCR and a specific antigen, but was mediated by DC-derived IL-12. Reciprocally, Vgamma1 T cells provided a key cytokine, IFN-gamma, which increased IL-12 production by BCG-infected DC. Moreover, exposure of BCG-infected DC to Vgamma1 T cells conditioned the former to prime a significantly stronger anti-mycobacterial CD8 T cell response. Consequently, stimulation of gammadelta T cells and their non-cognate interaction with DC could be applied as an immune adjuvant strategy to optimize vaccine-induced CD8 T cell immunity.     

All roads lead to Rome: triggering dendritic cell migration

Migration of dendritic cells to secondary lymphatic organs is a key event in acquired immunity. The role of the multifunctional ectoenzyme CD38 in humoral immune responses has now been revisited, suggesting that CD38 links innate and adaptive immunity by triggering chemokine-mediated dendritic cell chemotaxis.     

结核分枝杆菌Ag85A基因DNA疫苗的构建及其联合人IL-12表达质粒诱导的小鼠细胞免疫应答观察

目的:构建编码结核分枝杆菌Ag85A分泌蛋白重组真核表达质粒,研究其与hIL-12联合免疫小鼠后的细胞免疫应答。方法:(1)构建质粒:采用PCR法从H37Rv菌株中扩增Ag85A编码基因,用限制性内切酶消化后,插入克隆载体PMD20-T中,经酶切鉴定与序列测定证实后,以亚克隆法构建于真核表达载体PCDNA3.1的相应酶切位点。(2)动物实验:50只C57BL/6N小鼠随机分为:①Ag85A基因疫苗+hIL-12质粒组(联合免疫组);②重组Ag85A基因疫苗组;③卡介苗BCG组(阳性对照);④空载体组(阴性对照);⑤PBS组(空白对照)。基因疫苗、空载体和PBS经肌内注射法免疫各组小鼠,每隔3周免疫1次,共免疫3次,BCG组经尾部皮下注射1×106CFU BCG免疫1次,约0.3 ml/只。第三次免疫小鼠后28天,处死各组小鼠,分离脾细胞,ELISA法检测脾细胞培养上清液中IFNγ-、IL-2、IL-4水平;乳酸脱氢酶释放法检测脾细胞杀伤活性;分离的脾细胞经TB-PPD刺激后,XTT比色法检测脾淋巴细胞增殖活性。结果:(1)成功构建结核分枝杆菌Ag85A基因DNA疫苗。(2)联合免疫组能诱导较强烈的抗原特异性Th1型细胞免疫应答,免疫小鼠脾细胞培养上清液IFN-r和IL-2水平显著高于Ag85A基因疫苗组,与BCG组相当,IL-4分泌减少;特异性CTL杀伤活性明显增强;淋巴细胞增殖活性也明显高于其他组别。结论:hlL-12表达质粒能够增强结核分枝杆菌Ag85A基因DNA疫苗所诱导的小鼠免疫应答。