树突状细胞在多发性硬化免疫治疗中的展望

树突状细胞（DC）是体内最强大的递呈细胞，在机体免疫系统中发挥着重要的免疫调节作用。近年，人们已经发现它在多发性硬化（MS）中具有致病性和促恢复性的双重作用，而且通过体外培养环境的调控可以改变其功能和DC类型。本文就DC在MS中已经取得的成果、研究热点和其治疗前景作一综述。     

树突状细胞在多发性硬化免疫治疗中的展望

树突状细胞 (DC)是体内最强大的递呈细胞 ,在机体免疫系统中发挥着重要的免疫调节作用。近年 ,人们已经发现它在多发性硬化 (MS)中具有致病性和促恢复性的双重作用 ,而且通过体外培养环境的调控可以改变其功能和DC类型。本文就DC在MS中已经取得的成果、研究热点和其治疗前景作一综述。     

036 树突状细胞在多发性硬化免疫治疗中的展望

树突状细胞(DC)是体内最强大的递呈细胞，在机体免疫系统中发挥着重要的免疫调节作用。近年，人们已经发现它在多发性硬化(MS)中具有致病性和促恢复性的双重作用，而且通过体外培养环境的调控可以改变其功能和DC类型。本文就DC在MS中已经取得的成果、研究热点和其治疗前景作一综述。     

人血树突状细胞与单核细胞的比较观察

对人血树突状细胞和单核细胞的光镜、透射电镜和扫描电镜观察表明：Ｇｉｅｍｓａ染色两菜态似；但树突状细胞呈Ｓ－１００蛋白阳性，Ｌｙｓｏｚｙｍｅ阴性，细胞表面光滑，有各种突起，细胞器很少。而单核细胞呈Ｌｙｓｏｚｙｍｅ阳性，Ｓ－１００蛋白阴性，细胞表面有微绒和微皱褶，细胞器发达，特别是有大量溶酶体。扫描电镜和透射电镜检查也有鉴别意义。     

颈动脉粥样硬化患者中血管平滑肌细胞的变化

目的探讨血管平滑肌细胞(VSMCs)在颈动脉粥样斑块中的数量与分布,为临床分析颈动脉粥样硬化斑块的稳定性提供理论依据。方法对68例颈动脉内膜剥脱术(CEA)患者的斑块,采用Movat染色和免疫组化方法检测斑块中VSMCs,镜下分别统计VSMCs平均积分吸光度值(MA)、单位面积的MA和纤维帽厚度。结果无症状组稳定性和不稳定性斑块发生率为87.5%和12.5%(P0.001);症状组为25.0%和75.0%(P0.001)。VSMCs在无症状组和症状组中的MA值分别为1 650±58和1 343±54(P0.001);在稳定和不稳定性斑块中分别为1 506±59和1 312±58(P0.05)。无症状组和症状组中VSMCs分布单位面积的MA分别为:基底部1 664±73(MA/mm~2)、1 112±69(MA/mm~2)(P0.001);肩部1 697±76(MA/mm~2)、1 412±81(MA/mm~2)(P0.05);纤维帽1 620±65(MA/mm~2)、1 321±66(MA/mm~2)(P0.01)。随着纤维帽的增厚,VSMCs的单位面积的MA也随之增加,呈正相关性(P0.001)。结论症状组和不稳定性斑块中VSMCs的数量、密度均少于无症状组和稳定斑块。纤维帽的厚度与VSMCs的密度呈正相关性。     

人外周血CD4~+树突状细胞的纯化及鉴定

目的　建立人外周血树突状细胞 (dendriticcell,DC)的分离方法 ,观察其形态学和免疫组织化学特点 ,为下一步细胞融合提供DC来源。方法　以免疫磁珠分选法从人外周血单个核细胞中分离CD4 + DC ,流式细胞仪检测所得细胞的纯度 ,光镜、电镜和激光共聚焦扫描显微镜观察其形态 ,SP免疫细胞化学方法检测DC的分子表达。结果　此纯化方法所得细胞纯度可达到 80 %以上 ,形态学观察可见纯化细胞具有典型的DC特征 ,该细胞能高表达HLA DR和S 10 0分子。结论　免疫磁法可获得较高纯度典型DC ,为进一步进行DC与肿瘤的融合实验及临床应用提供了可能     

树突状细胞与趋化因子的研究进展

树突状细胞(dendritic cell,DC)是功能最强的抗原提呈细胞,广泛存在于多种器官和组织中。DC前体来源于骨髓CD34^ 细胞,随血液循环分布到抗原可能入侵的部位。这些不成熟DC能持续而有效地吞噬抗原,高表达MHC Ⅰ类、Ⅱ类分子以及协同刺激分子,随后进入脾脏或淋巴结并成熟。成熟DC吞噬作用下降,协     

树突状细胞在病毒性心肌炎中的作用及其可能的机制

病毒性心肌炎的发病机制尚不完全清楚,病毒感染后引起的免疫损伤作用可能是其重要机制之一.树突状细胞是功能强大的专职抗原提呈细胞,连接固有免疫反应和适应性免疫反应,居于免疫反应的中心地位.树突状细胞在病毒性心肌炎中的作用及其机制目前还没有相关报道.本文就病毒性心肌炎的免疫学发病机制以及树突状细胞的生物学特性和其在病毒性心肌炎免疫学发病中的作用作一综述,旨在为心肌炎的治疗提供新方向.     

树突状细胞亚群在动脉粥样硬化中的作用

动脉粥样硬化是一种免疫相关的大中动脉的慢性炎症性疾病。固有免疫应答和适应性免疫应答均参与动脉粥样硬化的发生,树突状细胞(DC)是联系固有性免疫和适应性免疫的桥梁,在启动机体免疫应答和维持免疫耐受中处于中心地位。本文综述了动脉壁中的DC亚群组成以及DC亚群在动脉粥样硬化炎症免疫中的作用,包括摄取脂质、释放细胞因子和通过调控T细胞从而影响动脉粥样硬化的发生发展,并总结了基于DC疫苗在防治动脉粥样硬化中的研究现状和展望。     

树突状细胞在人巨细胞病毒感染中的作用

人巨细胞病毒(human cytomegalovirus,HCMV)在人群中感染率极高,通过多种免疫逃避机制,实现在宿主体内的长期潜伏感染。树突状细胞(dendritic cells,DC)是重要的抗原提呈细胞,在诱导和维持特异性免疫应答中发挥重要的作用。人体内的DC根据来源、表型分为两群:髓系DC(myeloid DC,mDC)和浆细胞样DC(plasmacytoid DC,pDC),大量研究证实HCMV介导的多种免疫逃避机制中,部分是通过影响DC功能实现的。HCMV不仅可以感染mDC,影响mDC表型、迁移、分泌细胞因子、激活T细胞功能,而且还可以抑制pDC分泌干扰素水平及激活T细胞能力,并且激活过度的B细胞反应,导致机体抗病毒细胞免疫反应的抑制和体液免疫紊乱,实现病毒长期潜伏感染。本文主要讨论HCMV是如何改变两种DC亚型的功能以实现免疫逃避目的。     

The expression of vascular dendritic cells in human atherosclerotic carotid plaques

Atherosclerosis is currently considered a chronic inflammatory disease, and evidence is accumulating for a role of the immune system in the progression of atherosclerosis. Dendritic cells are specialized antigen-presenting cells with the unique ability to initiate a primary immune response to certain antigens by the activation of naive T-lymphocytes. Although dendritic cells are well known to be important in the development of different diseases, studies of vascular dendritic cells in atherosclerosis are rare, and their role is not clearly understood. Therefore, we investigated the immunohistochemical expression of vascular dendritic cells in atherosclerotic plaques. Between April 2003 and December 2005, carotid endarterectomy was performed in 26 consecutive patients, and 27 carotid plaque specimens were analyzed. We investigated the immunohistochemical expression of vascular dendritic cells in human carotid plaques by measuring the signal intensity of fascin-positive cells using an image analyzer. In addition, these immunohistochemical results were related to clinical data. The highest signal intensity of dendritic cells was found in plaque shoulders, and the mean signal intensity of dendritic cells was significantly higher in complicated than in uncomplicated plaques (P = .0029). Moreover, the mean signal intensity of dendritic cells in plaques from symptomatic patients was significantly elevated compared with plaques from asymptomatic patients (P = .0004). Although atherosclerotic plaque instability is determined by multiple factors, the immune and inflammatory pathways play a particularly important role. Dendritic cells play a role in atherosclerosis, and the present study suggests that the expression of dendritic cells in human carotid arteries may be strongly associated with the occurrence of ischemic stroke.     

Human atherosclerotic plaques express DC-SIGN,a novel protein found on dendritic cells and macrophages

The association of autoimmune phenomena with atherosclerosis suggests that plaques may contain specialized antigen-presenting cells, dendritic cells (DCs). DC-SIGN is a C-type lectin expressed by DCs. This study assessed whether human atherosclerotic plaques expressed DC-SIGN and several other macrophage/DC markers. Plaques from human coronary and carotid arteries and aorta contained DC-SIGN-immunoreactive cells. Double-labelling showed co-expression of DC-SIGN and macrophage/DC lineage markers CD14, CD68, HLA-DR, and S100. There was no immunoreactivity for the DC activation markers CD83 or CMRF-44. Since DC-SIGN mediates adhesion to T-lymphocytes and endocytosis, its expression in atherosclerotic plaques may have functional implications. Activated DCs migrate quickly from areas of inflammation to regional lymph nodes, possibly explaining the paucity of activated DCs in atherosclerotic plaques. In conclusion, this study has shown that DC-SIGN is expressed in atherosclerosis.     

Immunohistochemical localization of C-reactive protein-binding sites in human atherosclerotic aortic lesions by a modified streptavidin-biotin-staining method

One-step fluorescein-conjugated polyclonal antibody technique has shown that C-reactive protein (CRP) was located only extracellularly in human atherosclerotic lesions. In this report a more sensitive streptavidin-biotin technique was applied to detect the localization of CRP in human athere sclerotic lesions. lmmunohistochemical staining with polyclonal and monoclonal anti-human CRP antibodies both produced a brown color extracellularly in the necrotic lesions, and intracelluarly in CD68+ foam cells. The latter suggests an uptake of CRP-lipid complexes by macro-phages. The staining is human CRP-specific because it was eliminated by preabsorption of the monoclonal antibody with pure human CRP, or by substitution of the primary antibody with non-immune rabbit serum. By overlaid CRP-binding study, a positive stain was observed on intimal smooth muscle cells and foam cells, suggesting that they have CRP-binding sites unless the CRP-binding activity was generated de novo through the fixation procedure. Accordingly, it is hypothesized that CRP may facilitate the uptake of lipids by macrophages accumulating in atherosclerotic lesions. Further, CRP might participate in cytolysis, which enlarges the necrotic area, and/or in phagocytosis that scavenges the necrotic tissue.     

Endothelial cilia in human aortic atherosclerotic lesions

Summary Primary cilia were present in the endothelial cells of human aortic fatty dots and streaks but not in those of normal intima. They had the features of cilia of the 9+0 axonemal configuration observed in many other cells. A lateral foot process and transitional fibers anchored the ciliary basal body in the cytoplasm, but rootlets were not identified in material examined. Ladder-like configurations interconnected the two centrioles (=diplosome) of control endothelium.The primary cilia of endothelium differed from those of the rudimentary type observed in smooth muscle cells in similar lesions of man, but shared many features with cilia of those present in experimental atherosclerosis in rabbit.Cilia were rarely described in vascular endothelium. It is believed that, to date, they were not reported to occur in normal or pathological arteries in man.It is being stressed that whereas the significance of these unusual organelles remains uncertain, their widespread occurrence may indicate that their role is more important than was believed previously, and they should cease being a curiosity only.Presented-in-part at the Workshop of the American Heart Association: Evolution of the Human Atherosclerotic Plaque, Rockville, Maryland, September 20–23, 1986.Dedicated to Professor Dr. Gotthard Schettler, Department of Internal Medicine, University of Heidelberg, FRG, on the occasion of his 60 birthday (April, 1987).     

人外周血树突状细胞-乳腺癌细胞融合细胞

目的：探讨树突状细胞—肿瘤细胞融合细胞的形态特性，为研制融合细胞疫苗提供形态学依据。方法：将免疫磁珠法分离的人外周血树突状细胞与人乳腺癌细胞株MCF7融合，瑞氏—姬姆萨染色观察；扫描电镜观察树突状细胞、融合细胞的表面超微结构。结果：树突状细胞与MCF细胞按10：1比例融合后，一个乳腺癌细胞可以与一个或多个树突状细胞相融合；扫描电镜下可见分离的树突状细胞表面有突起，树突状细胞/MCF7融合细胞具两种亲代细胞的表面超微结构特点。结论：树突状细胞与人乳腺癌细胞融合后无明显的形态改变。     

浆细胞样树突状细胞与疾病

目前对于浆细胞样树突状细胞(pDC)的来源、分布和功能研究不断深入,对于pDC在疾病发病、诊断、治疗中的作用正越来越受到关注。本文综述了pDC与抗病毒免疫特别是HIV感染、肿瘤、自身免疫病的关系,并总结了目前所发现的可以调控pDC生成和功能的药物,希望能为某些疾病的防治提供新的思路和方法。     

Distinct compartmental distribution of mature and immature dendritic cells in esophageal squamous cell carcinoma

Dendritic cells (DCs) play a critical role in generating anti-tumor immunity. DC functional defect has been related to the growth and progression of various human cancers. In esophageal squamous cell carcinoma (ESCC), the examination of DCs using immunohistochemistry (IHC) with anti-S100 antibody has demonstrated an increased infiltration of DCs into the tumor mass, however, the distribution patterns of DCs at different maturation states in ESCC are not fully evaluated. In this study, we immunohistochemically analyzed the DC maturation status by examining the S100-positive DCs, CD1α-positive immature DCs (iDCs), and CD208-positive mature DCs (mDCs) and their distribution patterns in 45 ESCCs and 10 control tissues. The IHC analysis showed that the number of S100-positive DCs was increased in both the cancer epithelium and tumor stroma. Further phenotypic analyses revealed that intraepithelial DCs in the cancer mass were predominantly CD1α-positive iDCs. Whereas DCs presented in the tumor stroma were exclusively CD208-positive mDCs, CD208-positive mDCs were particularly dense in the margin of cancerous lesions and formed clusters with CD3-positive lymphocytes. The number of CD208-positive mDCs in the tumor mass was significantly lower than the number of CD1α-positive iDCs. The current results suggest that ESCC tissue comprises a high frequency of iDCs in the cancerous epithelium and a low density of mDCs in the tumor stroma. Such a distinct distribution pattern may reflect the ongoing DC tracking in ESCCs.     

An improved method for purifying human thymic dendritic cells

Thymic dendritic cells (DC) play a prominent role in the immune response as they constitute a key element involved in the maturation of thymocytes in the thymus. Human thymic DC, like DC from other lymphoid organs, represent a minor cell population (< 2%) of the thymus. Since these cells cannot replicate in vitro, the development of efficient purification methods is an essential prerequisite for extensive functional studies. DC express high levels of HLA-DR, a cell surface marker of the MHC class II antigen which is not exclusive to DC. Since no specific human thymic DC marker has been identified so far, DC purification methods are mainly based on depletion of particular subgroups of cells. We report here an improved method for purifying human thymic dendritic cells. In contrast to prior work, CD2⁺ thymocytes were first depleted by rosetting with neuraminidase treated sheep red blood cells. The nonrosetted cells were separated in a Percoll gradient, and the low-density cells were subsequently depleted of nondendritic cells by using thymocyte and macrophage specific monoclonal antibodies and either magnetic bead depletion or cytofluorometry. Cell populations (18–55 × 10⁶ cells) obtained following magnetic bead purification were at least 80% HLA-DR⁺/CD2⁻ and exhibited ultrastructural morphological features and functional activities such as those described previously for thymic DC. This improved method was compared with different purification approaches that use various combinations of cell density-based separation techniques and cell surface specific markers antibody reactivity. The magnetic beads depletion approach provided higher yields.     

乳腺导管内增生性病变及浸润性癌中树突状细胞的检测

目的　检测乳腺导管内增生性病变和微小浸润性癌及浸润性导管癌中树突状细胞(dendriticcells,DC)和T细胞的 分布状况和浸润密度,探讨乳腺癌发生、发展中机体免疫状态的变化规律。方法　应用免疫组化S P法和两步法对16例正常 副乳腺、58例导管内增生性病变、4例微浸润导管癌及67例浸润性导管癌乳腺标本进行S 100蛋白+DC、HLA DR+DC、CD1a +DC(DC三参数)及CD45RO+T细胞的浸润密度检测。结果　浸润癌中DC三参数浸润密度均高于其它病变组织(P< 0.05)。导管原位癌、微浸润癌及浸润癌组织中CD45RO+T细胞浸润密度均高于其它病变组织(P<0.05)。DC三参数间及 其与CD45RO+T细胞间均呈正相关(P<0.001)。结论　DC浸润密度随增生性病变加重而逐渐增高,发展为浸润癌时则明 显增高。