树突细胞的免疫调节功能及其影响因素(附视频)

树突细胞(DC)是体内功能最强的专职抗原呈递细胞,它在调控机体对自身或非自身抗原产生适当的免疫应答方面起非常重要的作用.DC是一群异质性的细胞,不同亚型的DC具有不同的功能.组织微环境、DC的成熟状态、DC表面的免疫分子以及局部组织基质细胞 (如肝星状细胞) 等与DC的功能有关.通过改变DC表面的一些关键分子的表达能够调控DC诱导的免疫反应.阐明决定DC诱导免疫耐受功能的关键分子以及DC选择性触发T细胞向Th1/Th2/Th17/Treg等不同方向分化的关键因素对寻找用新的方法来调控机体免疫反应具有重大意义.     

树突状细胞与肝癌免疫治疗进展

树突状细胞 (dendritic cells,DC)是指具有树枝状形态 ,膜表面高表达 MHC 和 类分子以及多种辅助分子 (如CD5 4、CD80、CD86等 ) ,能有效摄取、加工和处理抗原并激活初始型 T细胞的一类细胞。作为目前发现的功能最强的专职抗原提呈细胞 (antigen presenting cells,APC) ,DC是抗原特异性免疫应答的始动者 ,在调控机体的免疫应答以及抗肿瘤过程中发挥重要作用。肝细胞癌 (HCC)是高度恶性肿瘤之一 ,目前尚缺乏有效的治疗。以 DC为基础的肝癌免疫治疗日益受到重视 ,取得了初步成果。本文就 DC在肿瘤免疫中的作用机制及其应用于 HCC…     

细胞因子对树突状细胞成熟的调节作用及机制

树突状细胞(dendritic cell,DC)是目前所知的体内功能最强的专职抗原呈递细胞,是机体免疫反应的始动者,在免疫应答诱导中占有独特的地位.研究DC的调节机制,通过调节其功能来调控机体的免疫应答过程,对感染、肿瘤、移植排斥、自身免疫性疾病发生机制的认识和防治措施的制定具有重要意义.     

LAP+CD4+T细胞的研究进展

【摘要】 调节性T细胞是机体维持自身稳定的重要组成部分,对免疫反应具有抑制效应,在阻止自身免疫反应和维持机体免疫平衡等方面均具有重要作用。现在已发现不同的具有调节功能的T细胞亚群,如CD4+CD25+T细胞、Th3细胞和Tr1细胞等,这些T细胞多通过产生具有抑制功能的细胞因子,如IL-10和TGF-β等发挥免疫抑制效应。LAP+CD4+T细胞是近年发现的一种新的调节性T细胞亚群,在体内外实验中被证实具有免疫抑制作用,它通常以依赖TGF-β和IL-10等细胞因子的方式来发挥作用,且在一些疾病的动物模型中它影响着疾病的发生、发展,如自身免疫性疾病,炎症型疾病等。较少的研究提示LAP+CD4+T细胞在癌症病人中具有促进肿瘤进展的作用。     

核转录因子-κB信号途径调节树突状细胞功能的研究进展

树突状细胞（DC）广泛分布于机体免疫器官和外周免疫组织中,是目前已知功能最强大的专职性抗原提呈细胞。DC能够启动初次免疫应答,同时也是重要的免疫辅助细胞,对建立T细胞特异性免疫应答和调控免疫反应起关键作用。核转录因子-κB（NF-κB）在DC的分化、发育、成熟及调节其免疫功能中起到重要的作用,基于NF-κB信号通路的DC免疫治疗逐渐受到关注。现对这一方面的研究进展综述如下。     

耐受性树突状细胞的研究进展

树突状细胞(DC)是已知最强的抗原呈递细胞，在机体内可诱导强烈的免疫反应。但随着对DC深入研究发现，DC的来源、表型及其功能都具有明显的多样性和异质性。DC既可以刺激免疫反应，也可诱导免疫耐受，目前对其机制不甚清楚。最近有人提出耐受性DC的概念。     

耐受性树突状细胞的研究进展

树突状细胞 (DC)是已知最强的抗原呈递细胞 ,在机体内可诱导强烈的免疫反应。但随着对DC深入研究发现 ,DC的来源、表型及其功能都具有明显的多样性和异质性。DC既可以刺激免疫反应 ,也可诱导免疫耐受 ,目前对其机制不甚清楚。最近有人提出耐受性DC的概念     

树突状细胞疫苗与肝癌免疫治疗进展

以肿瘤疫苗为基础的主动免疫治疗和以T细胞介导的抗肿瘤免疫应答成为肿瘤治疗新的热点,近来发现,肝癌患者癌灶缺乏成熟而有活性的CD8+树突状细胞(dendriticcells,DC),表明肝癌发生过程中有活性DC的浸润作用[1]。DC是机体免疫系统中功能最强的专职性抗原提成细胞(Antigen-presentingcells,APC),其最大特点是能激活初始型T细胞(CD4+Th细胞和CD8+CTL细胞),生成辅助性T细胞和杀伤性T细胞,DC能识别、加工、提呈抗原,表达高水平MHC类分子,共刺激分子,粘附分子,同时分泌高水平的IL-12,从而主导初始型T细胞生成Th1型应答,Th1型应答在…     

树突细胞与移植免疫

树突细胞 (dendriticcell,DC)以其表面具有星状多形性或树枝状突起而得名 ,首先在淋巴组织中被发现 ,随后在很多非淋巴组织中发现 ,包括血液、骨髓、肝脏、脾脏、皮肤、气道、内脏粘膜等 ,并发现该细胞与移植免疫关系密切。1　DC的表型与分类DC不是单一的细胞类型 ,它是不同细胞类型的复杂混合体。小鼠DC公认的表型为MHCⅡ +、CD11c+、B7 2 +、CD4 0 +、HAS+、CD3、CD4、B2 2 0、Ig。早期通过CD8的表达与否来分类 ,发现小鼠的胸腺有两类DC ,考虑分别来源骨髓和淋巴[1,2 ] 。髓系DC通常触发免疫反应 ,诱导Th1细胞的分化 ;而淋巴…     

树突状细胞疫苗抗骨肉瘤免疫治疗

树突状细胞(dendritic cell, DC)是体内最重要、功能最强大的专职抗原递呈细胞(APC),且是机体内唯一能激活初始T淋巴细胞的APC,可有效触发诱导细胞毒性T细胞免疫应答。DC参与抗原摄取、加工处理和递呈。以DC为主特别DC疫苗的抗肿瘤疗法已取得令人鼓舞的进展。然而,DC疫苗目前还存在一定的局限性。骨肉瘤抗原异常表达、MHC-I分子下调以及肿瘤微环境中高浓度免疫抑制因子的存在等原因使得骨肉瘤发生免疫逃逸,限制了DC疫苗的应用。本文现就以DC疫苗及骨肉瘤相关免疫治疗基础进行综述。     

Plasmacytoid Dendritic Cells: No Longer an Enigma and Now Key to Transplant Tolerance?

Plasmacytoid (p) dendritic cells (DC) are a specialized subset of DC whose primary role was initially defined by the production of type I interferons in response to viral infection. They are now known to also possess a repertoire of functions capable of determining T cell fate and activation. Under homeostatic conditions, non‐lymphoid tissue‐resident pDC play a critical role in the regulation of mucosal immunity, as well as the development of central and peripheral tolerance. Although these cells display a number of characteristics that differ from conventional DC, particularly altered costimulatory molecule expression and poor allostimulatory capacity when interacting with T cells, this phenotype favors the generation of alloantigen‐specific regulatory CD4⁺ or CD8⁺ T cells critical to the development of graft tolerance. In this minireview, we discuss pDC ontogeny, functional biology and the emerging data that demonstrate the importance of pDC in the induction of tolerance, as well as recent studies that define mechanisms underlying pDC‐mediated tolerance to both solid organ and haematopoietic stem cell transplants. We also highlight their use in clinical settings and the potential of pDC both as targets and cellular therapeutic agents to improve the outcome of organ transplantation.     

大鼠未成熟树突状细胞体外扩增及功能鉴定

摘要：目的 探讨建立大鼠体外大量扩增未成熟树突状细胞(DC) 的方法, 以及不同剂量粒细胞巨噬细胞集落刺激因子(GM CSF)对大鼠DC分化成熟的影响。方法 分离纯化并扩增大鼠骨髓细胞，用不同剂量GM CSF培养,6 d 和10 d后收集悬浮细胞进行扫描电镜观察和免疫表型鉴定,并行混合淋巴细胞反应,观察其诱导未致敏T 淋巴细胞增殖的情况。结果 小剂量GM CSF 培养获得的DC(GMlowDC) 形态上具有DC 的典型特征,在细胞表型、细胞功能试验上具有未成熟的特性,具有DC 的典型特征,细胞表面高表达CD11c,低表达CD80，CD86及MHC II类分子,与大剂量GM CSF加IL 4的联合组培养获得的DC( GMhighDC) 相比,其体外刺激未致敏T 淋巴细胞的增殖能力较弱.结论 笔者所建立的培养未成熟DC 的方法是可行的；GM CSF的剂量与细胞的成熟程度相关。     

小鼠骨髓未成熟树突状细胞体外扩增及鉴定

目的建立体外大量扩增小鼠未成熟树突状细胞(DC)的方法，从形态学、免疫表型和细胞功能试验等方面予以鉴定。方法制备小鼠骨髓细胞，分别用不同剂量重组小鼠粒细胞巨噬细胞集落刺激因子(rmGM—CSF)培养，7d后收集悬浮细胞进行扫描电镜观察和免疫表型鉴定，并行混合淋巴细胞反应，观察其诱导未致敏T淋巴细胞增殖的情况。结果小剂量rmGM—CSF培养获得的DC(GM^low DC)具有DC的典型特征，细胞表面高表达CD11c，低表达CD40、I—A／1-E，不表达B7—1，与大剂量rmGM—CSF培养获得的DC(GM^high DC)相比，其体外刺激未致敏T淋巴细胞增殖的能力较弱。结论本实验中获得的GM^low DC形态上具有DC的典型特征，在细胞表型、细胞功能试验上具有未成熟的特性，说明所建立的培养未成熟DC的方法是可行的；rmGM—CSF的剂量与细胞的成熟程度相关，一般说来，较大剂量的rmGM—CSF诱导生成的细胞以成熟。DC为主，小剂量rmGM—CSF诱导生成的细胞以未成熟DC为主。     

Identification and functional characterization of dendritic cells in the healthy murine kidney and in experimental glomerulonephritis

The kidney tubulointerstitium contains numerous bone marrow-derived antigen-presenting cells, which are often referred to as resident tissue macrophages, although several previous studies had demonstrated characteristics of dendritic cells (DC). In this study, we describe a subset of tubulointerstitial cells expressing the DC marker CD11c. A protocol was established to isolate these cells for in vitro analysis. Renal CD11c(+) cells resembled splenic DC, but not peritoneal macrophages, in morphology, lysosomal content, phagocytic activity, microbicidal effector functions, expression of T cell costimulatory molecules, and ability to activate T cells. Nevertheless, many CD11c(+) renal cells expressed low or intermediate levels of F4/80 and CD11b, indicating that both markers are not absolutely specific for macrophages in the kidney. Subpopulations of renal DC could be distinguished based on their expression of MHC class II and costimulatory molecules and may represent different maturation stages. In nephrotoxic glomerulonephritis, increased numbers of CD11c(+) cells showing DC functionality were found in the tubulointerstitium. Focal accumulation was seen within tubulointerstitial mononuclear infiltrates and adjacent to, but not within, inflamed glomeruli. These results are the first to identify and characterize renal CD11c(+) cells as DC and to demonstrate marked changes in experimental glomerulonephritis.     

携带供者抗原的第三方树突状细胞诱导小鼠皮肤移植耐受的研究

目的 了解携带供者抗原的第三方树突状细胞(DC)是否具有与供者源未成熟DC相似的免疫功能.方法 雌性C57BL/6小鼠、BALB/c小鼠和昆明小鼠分别为皮肤移植的供者、受者和第三方.将40只BALB/c小鼠分为对照组、环磷酰胺组、供者源未成熟DC组、第三方未成熟DC组、携带供者抗原第三方DC组,每组8只.后4组大鼠皮肤移植术前4 d用环磷酰胺(200 mg/kg)预处理,对照组同法给予等量等渗盐水.后3组术前2 d用1 ml相应DC悬液(1×107个/ml)预处理,并在术后12 d重复给予1 ml DC悬液(1×107个/ml)1次;前2组于上述2个时相点同法给予等量等渗盐水.记录各组皮片平均成活时间(MST)并于术后5 d对皮片进行组织学观察.结果 与对照组(16.1±3.5)d比较,供者源未成熟DC组和携带供者抗原第三方DC组小鼠移植皮片的MST明显延长,分别为(38.3±7.7)、(34.9±7.7)d(P＜0.01);携带供者抗原第三方DC组与供者源未成熟DC组皮片的MST相近(P＞0.05),但与第三方未成熟DC组(23.7±2.7)d比较,差异有统计学意义(P＜0.05).镜下见携带供者抗原第三方DC组移植皮片结构较清楚、排列有序,与供者源未成熟DC组情况相近.结论 携带供者抗原的第三方DC与供者源未成熟DC,均可在一定程度上建立抗原特异性免疫耐受.     

Dendritic Cells Promote Macrophage Infiltration and Comprise a Substantial Proportion of Obesity-Associated Increases in CD11c+ Cells in Adipose Tissue and Liver

Obesity-associated increases in adipose tissue (AT) CD11c(+) cells suggest that dendritic cells (DC), which are involved in the tissue recruitment and activation of macrophages, may play a role in determining AT and liver immunophenotype in obesity. This study addressed this hypothesis. With the use of flow cytometry, electron microscopy, and loss-and-gain of function approaches, the contribution of DC to the pattern of immune cell alterations and recruitment in obesity was assessed. In AT and liver there was a substantial, high-fat diet (HFD)-induced increase in DC. In AT, these increases were associated with crown-like structures, whereas in liver the increase in DC constituted an early and reversible response to diet. Notably, mice lacking DC had reduced AT and liver macrophages, whereas DC replacement in DC-null mice increased liver and AT macrophage populations. Furthermore, delivery of bone marrow-derived DC to lean wild-type mice increased AT and liver macrophage infiltration. Finally, mice lacking DC were resistant to the weight gain and metabolic abnormalities of an HFD. Together, these data demonstrate that DC are elevated in obesity, promote macrophage infiltration of AT and liver, contribute to the determination of tissue immunophenotype, and play a role in systemic metabolic responses to an HFD.     

PHENOTYPIC CHARACTERISATION OF THE DENDRITIC CELL INFILTRATE IN PROSTATE CANCER

Purpose

To investigate whether dendritic cells (DC), which as professional antigen presenting cells have the capacity to stimulate immune responses against tumour associated antigens, are recruited into and activated within prostate cancer.

Materials and Methods

Immunoenzyme and immunofluorescence labelling was used to identify leucocyte and DC subsets within 15 cases of prostate cancer. Cell numbers were compared with numbers in adjacent normal prostatic tissue. Total DC numbers were identified as CD45⁺ leucocytes not coexpressing any lineage specific markers. The Langerhans cell (LC) subset was detected using anti CD1a staining and activated DC were identified by their expression of either CD83, CD86 or CMRF44.

Results

DC were found to represent a small subset of leucocytes present in both benign and malignant prostatic tissue. Statistically there were significantly less DC and LC in prostate cancer compared with normal prostatic tissue. While only a small subset of DC expressed markers of activation in prostate cancer, this was significantly more than the virtual absence of activated DC in normal prostatic tissue.

Conclusions

This is the first time that DC have been studied in prostate cancer using the relatively new DC specific monoclonal antibodies CD83 and CMRF-44. These findings suggest that there is no active recruitment of DC into prostate cancer and those DC present are only minimally activated.     

衣霉素诱导内质网应激对树突状细胞成熟分化的影响

目的:内质网应激(ERS)是真核细胞中普遍存在的适应性应激反应,本研究应用ERS特异性诱导剂衣霉素(TM)体外刺激小鼠脾脏树突状细胞(DC),观察DC功能状态的改变情况.方法:分离正常BALB/c小鼠脾脏DC进行体外培养,给予ERS特异性诱导剂TM刺激,观察不同剂量、不同作用时间TM刺激与DC表面共刺激分子表达及分泌功...     

基因修饰的树突状细胞疫苗诱导抗肿瘤免疫

树突状细胞是目前已知最有效的专职抗原提呈细胞,能诱导针对肿瘤的特异性细胞毒性T淋巴细胞反应,在抗肿瘤免疫中发挥着重要作用.运用树突状细胞的这一特性制备的肿瘤疫苗在体外和体内实验都已证明其抗肿瘤效应.近年来,基因修饰的树突状细胞疫苗由于其更出色的抗肿瘤效应成为研究的热点.本文就目前基因修饰的树突状细胞疫苗的研究现状,包括...     

Osteoclasts in RA: Diverse origins and functions

Osteoclasts were recognized in the late 1990s as the cells responsible for generalized and focal bone loss in rheumatoid arthritis (RA). Concepts about osteoclast biology have changed radically based on recent evidence of considerable diversity in both the origins and the functions of osteoclasts. In addition, the role for osteoclasts is not confined to bone resorption but may also include active contributions to inflammatory and autoimmune responses. Thus, in RA, osteoclast progenitors may arise from both circulating cells and cells developed within the rheumatoid synovium or subchondral bone. Within the inflamed synovium, osteoclasts are activated by factors such as cytokines, immune complexes, or activators of the toll-like receptors, which are not found in healthy bone tissue. Finally, recent data suggest that osteoclasts may be capable of antigen presentation to T cells via major histocompatibility complex class I and class II molecules. Confirmation of this suggestion by future studies would indicate that osteoclasts might be involved not only in bone resorption, but also in autoimmune responses and antigen presentation. These data highlight the considerable complexity of interactions between bone tissue and the immune system. Research into these interactions may identify new targets for treatments against the bone abnormalities associated with chronic inflammatory disease.