抑制性树突状细胞诱导移植免疫耐受的研究进展

树突状细胞（DC）是功能强大的专职抗原呈递细胞。在器官或细胞移植中，DC通过直接或间接识别途径呈递抗原活化T细胞，引起移植免疫排斥反应，但某些特殊类型的DC也可以产生抑制免疫应答，促进免疫耐受的作用。基于DC这种生物学特性的异质性，目前有多种生物学策略诱生抑制性DC诱导移植免疫耐受。     

树突状细胞和免疫耐受

树突状细胞 (DC)是职业抗原递呈细胞 ,既可触发排斥反应 ,又能够调节T细胞反应而产生外周免疫耐受。尽管其诱导外周免疫耐受的确切机制尚不清楚 ,但DC在诱导供体特异性T无反应细胞 (Treg)凋亡 ,供体特异T调整细胞 ,转基因诱导耐受DC以及T辅助细胞转化方向等方面都取得了明显进展。进一步研究DC在诱导自身抗原耐受的作用机理 ,可以揭示DC诱导移植免疫耐受 ,以实现人类在不依赖免疫抑制剂的条件下产生供体特异性免疫耐受 ,本文拟就有关内容作一综述。     

树突状细胞和免疫耐受

树突状细胞（DC）是职业抗原递呈细胞，即可触发排斥反应，又能够调节T细胞反应而产生外周免疫耐受。尽管其诱导外周免疫耐受的确切机制尚不清楚，但DC在诱导供体特异性T无反应细胞（Treg）凋亡，供体特异T调整细胞，转基因诱导耐受DC以及T辅助细胞转化方向等方面都取得了明显进展。进一步研究DC在诱导自身抗原耐受的作用机理，可以揭示DC诱导移植免疫耐受，以实现人类在不依赖免疫抑制剂的条件下产生供体特异性免疫耐受，本文拟就有关内容作一综述。     

基因修饰树突状细胞诱导移植免疫耐受研究进展

在移植免疫反应中，树突状细胞(DC)作为专职抗原提呈细胞，既可活化T、B细胞生产免疫应答，同时某些类型DC由于缺乏共刺激分子或表达某些抑制性细胞因子而能诱导移植免疫耐受。针对DC提呈抗原及活化T、B细胞的多个环节，目前有许多策略将不同目的基因转染不同来源的DC，让其表达不同的表面分子或分泌免疫抑制因子，以诱导移植免疫耐受。     

树突状细胞与免疫耐受的研究进展

ＤＣ参与胸腺Ｔ细胞的阴性选择过程，也参与外周Ｔ细胞的致耐，ＤＣ可能是唯一具有胸腺Ｔ细胞阴性选择功能的细胞，在外周，ＤＣ通过“否决”效应，诱导Ｔ细胞失能及其他一些机制诱导耐受生成，本文就此方面研究予以综述。     

083 树突状细胞和免疫耐受

树突状细胞(DC)是职业抗原递呈细胞，既可触发排斥反应，又能够调节T细胞反应而产生外周免疫耐受。尽管其诱导外周免疫耐受的确切机制尚不清楚，但DC在诱导供体特异性T无反应细胞(Treg)凋亡，供体特异T调整细胞，转基因诱导耐受DC以及T辅助细胞转化方向等方面都取得了明显进展。进一步研究DC在诱导自身抗原耐受的作用机理，可以揭示DC诱导移植免疫耐受，以实现人类在不依赖免疫抑制剂的条件下产生供体特异性免疫耐受，本文拟就有关内容作一综述。     

树突状细胞与免疫耐受

树突状细胞是启动免疫反应的最重要的专职抗原递呈细胞,具有刺激初始型T细胞增殖、启动机体免疫反应并决定免疫应答方向的功能。不同分化状态、不同亚型的树突状细胞诱导不同方向的免疫应答。树突状细胞表面还存在与免疫耐受有关的抗原受体如:C型外源凝集素、整合素及Fc受体。     

树突状细胞与妊娠免疫耐受

正常妊娠胚胎作为半同种移植物之所以能够维持,取决于母胎界面免疫耐受的形成。树突状细胞（dendriticcells,DC）作为体内最重要的抗原提呈细胞,处于免疫应答的中心环节,不但具有激发免疫应答的能力,还可以下调免疫应答或诱导免疫耐受的产生。妊娠期间雌孕激素水平的改变也可能影响到树突状细胞的分化、成熟及功能,有利于妊娠的维持。本文就树突状细胞在妊娠免疫耐受中的作用作一综述。     

树突状细胞诱导外周免疫耐受的机制

树突状细胞既能启动免疫应答 ,又能诱导免疫耐受。目前对树突状细胞诱导外周耐受方面的研究进展迅速 ,本文就未成熟树突状细胞、免疫抑制因子处理的树突状细胞及转基因树突状细胞在诱导外周免疫耐受中的作用作一综述 ,这可能是治疗自身免疫性疾病和移植排斥反应的新途径     

Thymus‐homing dendritic cells in central tolerance

Central tolerance is critical in establishing a peripheral T‐cell repertoire purged of functional autoreactive T cells. One of the major requirements for effective central tolerance is the presentation of self and other innocuous antigens (Ags), including food, gut flora, or airway allergens, to developing T cells in the thymus. This seemingly challenging task can be mediated in some cases by ectopic expression of tissue‐specific Ags by thymic epithelial cells or by entry of systemic blood‐borne Ags into the thymus. More recently, thymic homing peripheral dendritic cells (DCs) have been proposed as cellular transporters of peripheral tissue‐specific Ags or foreign innocuous Ags. The aim of this viewpoint is to discuss the three principal thymic DC populations and their trafficking properties in the context of central tolerance. We will first discuss the importance of peripheral DC trafficking to the thymus and then compare and contrast the three DC subsets. We will describe how they were characterized, describe their trafficking to and their microenvironmental positioning in the thymus, and discuss the functional consequence of thymic trafficking and localization on thymic selection events.     

Mycophenolic acid inhibits maturation and function of human dendritic cells and B cells

Mycophenolic acid (MPA) is considered an immunosuppressive compound mainly because of its inhibitory effects on lymphocyte proliferation. Here we studied specifically the effects of MPA on the ability of dendritic cells (DCs) to activate T cells via the indirect pathway and on the maturation and function of B-lineage cells. We demonstrated that DC cell-surface receptors, associated with antigen uptake and antigen processing and presentation (CD83 and CD205), were differentially downregulated in the presence of MPA, translating into a decreased uptake of alloantigens and reduced stimulation of T cells with decreased cytokine secretion (interleukin (IL)-1Ra and transforming growth factor (TGF)-α). Similarly, MPA significantly inhibited B-cell differentiation into memory and plasma cells in vitro and decreased secretion of TNF-α, IL-1Ra, and IL-10. We further demonstrated for the first time that not only the amount of antibody secretion was significantly lowered in the presence of MPA but also the total number of antibody-producing cells was reduced. Importantly, we provide direct evidence that HLA-specific antibody secretion was also affected using a newly developed HLA antibody-specific B-cell enzyme-linked immunospot assay. Our data indicate additional pathways by which MPA downregulates the immune system. This in turn may lead to improved conditions for allograft tolerance and control of allograft rejection.     

胸腺中的树突状细胞与自身免疫耐受

树突状细胞作为一类重要的抗原提呈细胞,不仅能激发免疫应答,而且在中枢免疫耐受和外周免疫耐受中发挥着重要作用.胸腺中树突状细胞分为淋巴源性和髓源性,参与效应性T细胞的阴性选择和调节性T细胞的阳性选择过程.本文就胸腺内树突状细胞的来源、特点以及在中枢耐受中的机制作一综述.     

基因修饰未成熟树突状细胞诱导移植耐受的研究进展

未成熟树突状细胞(iDC)诱导同种异体移植耐受的能力有限,它可能在活体内复杂的微环境中接受成熟信号而被诱导成熟,而具有免疫抑制功能的单基因修饰iDC可增强其诱导同种异体移植耐受的能力,但仍有一定的局限性.因而有选择的联合不同具有免疫抑制功能的基因修饰iDC可显著增强iDC诱导同种异体移植耐受的能力.     

Phenotype and function of dendritic cells of patients with systemic lupus erythematosus

Dendritic cells (DC) regulate the activation and differentiation of T cells. They are activated by signals of inflammation and tissue damage, and thus could play a role in the amplification and perpetuation of autoimmune diseases such as systemic lupus erythematosus (SLE). Here we analyzed the phenotype of circulating DC from patients with SLE and studied their differentiation from monocytes. Peripheral blood DC exhibited increased levels of activation in patients with SLE. Although their in vitro differentiation process occurred normally, their responses to activation stimuli (LPS, TNF-α plus PGE(2), anti-CD40) were abnormal when compared to DC differentiated from healthy monocytes. When incubated in the presence of IL-10, DC from patients with SLE were able to induce tolerance to allogeneic antigens in a normal manner. Our results suggest that DC from patients with SLE are abnormal, in part due to the effect of abundant pro-inflammatory signals, but also because of intrinsic cellular defects that alter their responses to activation stimuli.     

人外周血单核细胞来源树突状细胞的成熟诱导

目的：探讨诱导树突状细胞成熟的最优方法。方法：以细胞因子GM-CSF和IL-4体外诱导人单核细胞来源的树突状细胞，分别采用CD40L、LPS、TNF-α、细胞因子鸡尾酒法（TNF-α、IL-6、IL-1β、PGE2）诱导成熟，24小时后收获DCs以流式细胞仪检测其成熟表型CD80、CD83、CD86、HLA-DR和FITC-Dextran的内吞能力，ELISA法检测其IL-12的分泌，MTT法检测其刺激淋巴细胞增殖活性。结果：CD40L、LPS、TNF-α、鸡尾酒法均可诱导DCs的成熟，其中以鸡尾酒法诱导成熟的效果最优，CD83的表达率为66.91%（P〈0.05）；成熟DCsFITC-Dextran的内吞能力明显下降；成熟DCsIL-12分泌量明显高于未成熟DCs，其中鸡尾酒法诱导成熟的DCs的IL-12分泌量最高，成熟的DCs有较强的刺激淋巴细胞增殖能力。结论：细胞因子鸡尾酒法是诱导DCs成熟的最佳方法。     

树突状细胞在结核病免疫应答中的作用及机制

作为最有效的专职抗原提呈细胞（DC）,树突状细胞在结核病免疫中的作用日益受到关注。机体感染结核杆菌后,未成熟DC（iDC）捕获抗原并逐渐发育成熟,携带抗原成份从感染组织迁移至外周免疫器官,将抗原成份提呈给T、B淋巴细胞激发免疫应答,起着连接固有免疫和适应性免疫作用,并通过分泌IL-12、IFN-γ等细胞因子参与机体免疫调节。深入研究DC在结核病免疫中的作用机制将为抗结核新型疫苗的开发及免疫治疗方案的设计提供依据。     

Respiratory dendritic cells: mediators of tolerance and immunity

The respiratory tract is under constant bombardment from both innocuous and pathogenic material. The decision of how to respond to these challenges is mediated by a specialized set of antigen presenting cells within the lungs called dendritic cells (DC). Proper respiratory homeostasis requires that these respiratory DC (rDC) utilize both the local lung inflammatory environment as well as recognition of pathogen-specific patterns to determine whether to maintain homeostasis by either driving tolerance or immunity to the inhaled material. This review will focus on rDC and highlight how rDC regulate tolerance and immunity.     

Toll样受体与树突状细胞

Toll样受体(TLR)在介导固有免疫和适应性免疫应答中有重要作用,可以表达于多种免疫细胞,包括树突状细胞(DC).了解Toll样受体的免疫学基础、与DC之间的联系以及其在免疫耐受干预方面的作用很有必要.