树突状细胞在支气管哮喘中的作用研究进展

支气管哮喘是由多种免疫细胞和炎性细胞因子参与发病的免疫系统性疾病。在支气管哮喘免疫过程发生的初始和维持阶段，树突状细胞对于过敏原的识别，摄取和提呈，CD4^＋T辅助细胞的分化和活化，以及气道变态反应和机体免疫耐受等方面发挥关键作用。通过干预树突状细胞在支气管哮喘发病机制中的作用，来达到治疗支气管哮喘的目的，已经成为目前指导临床用药的研究热点。     

炎性树突状细胞的功能特性及在支气管哮喘发病机制中的作用

树突状细胞是功能最强的专职抗原递呈细胞,作为机体免疫应答的启动者在免疫应答中占有重要地位.研究显示在感染或炎症状态下由炎性单核细胞分化而来的一种树突状细胞亚型——炎性树突状细胞,参与调节免疫应答.近来,炎性树突状细胞在支气管哮喘发生机制中的作用备受关注,现就炎性树突状细胞在不同类型免疫应答的作用及其与支气管哮喘的关系作一综述.     

树突状细胞在支气管哮喘中的研究进展

支气管哮喘（bronchialasthma,简称哮喘）是由气道炎症细胞、结构细胞（如气道上皮细胞、树突状细胞等）和细胞组分共同参与的气道慢性炎症性疾病。其中树突状细胞（dendriticcells,DCs）是哮喘发病的始动者,能驱使CD4’幼稚T细胞活化并向Th2细胞方向分化,并在维持免疫反应和免疫耐受方面发挥关键的作用。因此,DCs在哮喘中的关键作用决定了其将成为防治哮喘的一个重要靶点。     

过氧化物酶体增殖物激活受体对哮喘患者树突状细胞免疫调控的影响

支气管哮喘是以Th1/Th2细胞比例失衡和Th2细胞优势分化为免疫学发病基础的慢性气道炎症性疾病。树突状细胞(DC)在哮喘发病中起重要作用,髓系DC(DC1)能促使支气管哮喘原始Th细胞向Th2细胞分化增殖,肺脏淋巴系DC(肺脏DC2)能诱导免疫耐受;过氧化物酶体增殖物激活受体-γ(PPAR-γ)能减轻哮喘气道炎症。因此,我们综述了PPAR-γ对哮喘患者DC免疫调控功能的影响,为哮喘的研究防治探索新思路。     

树突状细胞在支气管哮喘中的作用

支气管哮喘(哮喘)是一种气道慢性嗜酸粒细胞性炎症,而T细胞的激活、分化对其发病有重要作用。目前树突状细胞(DC)被认为是最有效的抗原呈递细胞(APC),能有效激活初始型(naive)T细胞,引起气道嗜酸粒细胞性炎症,本文就树突状细胞的形成、抗原呈递功能、对TH1/TH2分化的诱导以及其对哮喘的指导性防治作用等进行综述。     

胸腺基质淋巴细胞生成素与支气管哮喘

胸腺基质淋巴细胞生成素(TSLP)是一种由上皮细胞产生的白介素7样细胞因子,与靶细胞TSLP受体相互作用,可以激活骨髓源性树突状细胞,进而诱导一种特殊类型的炎症型Th2细胞反应,而与支气管哮喘(简称哮喘)相关的致病性T细胞正是这类炎症型T细胞.TSLP还可诱导肥大细胞分泌Th2细胞因子,参与哮喘的发病过程.     

树突状细胞在支气管哮喘的作用

支气管哮喘（哮喘）是一种气道慢性嗜酸粒细胞性炎症，而T细胞的激活，分化对其发病有重要作用，目前树突状细胞（DC）被认为是最有效的抗原呈递细胞（APC），能有效激活被始型（naive)T细胞，引起气道哮酸粒细胞性炎症，本文就树突状细胞的形成，抗原呈递功能，对TH1－TH2分化的诱导以及春对哮喘的指导性防治作用等进行综述。     

树突状细胞与支气管哮喘研究进展

树突状细胞(dendritic cells,DC)通过激活初始T细胞、诱导Th2免疫应答偏移和维持气道炎症,以及负性调节作用,影响支气管哮喘(哮喘)疾病的发生、发展,是哮喘免疫应答的启动者、参与者和调节者.DC在免疫应答中的关键地位提示我们它可作为防治哮喘疾病的一个重要靶点.     

1,25-二羟维生素D3与支气管哮喘

支气管哮喘的免疫机制受多种因素的调节,其中涉及到Th1/ Th2 平衡紊乱等因素.目前已知1,25-二羟维生素D3对于Th1细胞起主导作用的疾病中有着重要意义,但其对于Th2细胞起主导作用的疾病如支气管哮喘的作用目前还没有足够的研究.本文首先描述了1,25-二羟维生素D3对于哮喘气道炎症的影响,然后介绍了其对于CD4+调节T细胞的两个主要亚群:自然调节性T 细胞尤其是获得性调节性T 细胞的作用,接着介绍了1,25-二羟维生素D3对于树突状细胞DC的影响和作用,以及其对于T细胞迁移方面的影响.了解1,25-二羟维生素D3在支气管哮喘中的作用及免疫调节机制,有助于开拓哮喘治疗的新方法.     

香烟烟雾暴露对支气管哮喘大鼠OX-62、白介素12表达的影响

目的 研究香烟烟雾暴露对支气管哮喘(简称哮喘)大鼠肺组织树突状细胞(dendritic cell,DC)的特异性标记蛋白OX-62、血浆及支气管肺泡灌洗液(BALF)白介素12(IL-12)表达的影响,探讨吸烟加重哮喘的免疫学机制.方法 30只雄性Wistar大鼠随机分为对照组、哮喘组、暴露组;建立哮喘大鼠模型和哮喘大...     

Dendritic cells in patients with type I Gaucher disease are decreased in number but functionally normal

Gaucher disease is a lysosomal storage disorder, in which undigested glucosylceramide is deposited in the cytoplasm of mature macrophages, which accumulate in the bone marrow and the reticuloendothelial system. Dendritic cells are bone marrow-derived cells, specialized for the uptake, processing, transport and presentation of antigens to T-lymphocytes. We investigated peripheral blood dendritic cell-precursors, as well as the potential of peripheral blood monocytes and bone marrow-derived progenitor cells, to differentiate into mature dendritic cells in 12 patients with type I Gaucher disease. Results of the 10 adult patients were compared with those of 10 healthy volunteers, matched for age and sex. Six patients were anemic and 9 were thrombocytopenic, but none had severe bone disease. Both myeloid and plasmacytoid dendritic cells of patients with Gaucher disease, as well as the yield of the monocyte-derived dendritic cells, obtained after GM-CSF and IL-4 stimulation, were found significantly decreased, when compared to controls (myeloid dendritic cells: 0.19 +/- 0.07% vs. 0.34 +/- 0.10%, P = 0.009, plasmacytoid dendritic cells: 0.17 +/- 0.12% vs. 0.39 +/- 0.13%, P = 0.004, monocyte-derived dendritic cells: 4.8 +/- 3.5% vs. 8.3 +/- 3.2%, P = 0.036). However, the immunophenotypic profile of dendritic cells, estimated by CD1a, CD40, CD54, CD80, CD83 and HLA-DR expression, the endocytic and allo-stimulatory capacity of the immature, as well as of the TNF-alpha- or lipopolysaccharite-stimulated mature monocyte-derived dendritic cells, was similar to those obtained by healthy controls. In addition, bone marrow-derived CD34+ cells differentiated in the presence of GM-CSF, SCF, TNF-alpha and IL-4 into mature dendritic cells that did not differ in number, phenotype and allo-stimulatory activity from those of controls. Our findings suggest that patients with Gaucher disease exhibit mainly quantitative defects of their dendritic cells' system, demonstrated by decreased circulating dendritic cell precursors of both myeloid and plasmacytoid type. This finding may contribute to the poor immune response against infectious agents and an impaired immune surveillance, associated with an increased risk of developing a neoplastic disease.     

Graves病甲状腺内树突细胞与体液免疫紊乱的关系

目的　探讨Graves病(GD)甲状腺内树突细胞 (DC)与其体液免疫紊乱的关系。方法用抗S 100蛋白抗体SP免疫组化法对 34例GD和 5例正常对照甲状腺内的DC进行定位和半定量研究。用表达重组促甲状腺激素 (TSH)受体的人胚肾细胞检测术前血清中的甲状腺刺激性抗体(TSAb)。对甲状腺内DC的浸润密度与血清TSAb值进行相关分析。结果　正常甲状腺内未见DC,在所有被检GD患者的甲状腺内均可见到DC异常增多,且大多数DC与其周围甲状腺上皮细胞或间质浸润淋巴细胞密切接触。GD患者甲状腺内DC的浸润密度与血清TSAb值密切正相关 (r=0 4461,P<0 01)。结论　GD患者甲状腺内异常增多的DC与其体液免疫紊乱有密切关系,在其自身免疫反应的发生发展中起着重要作用。     

Role of dendritic cells in atherosclerosis

Atherosclerosis is a lipid-related chronic inflammatory disease in which immune mechanisms play a pivotal role. The lesions are filled with large numbers of immune cells. During the last decade, dendritic cells have been identified in atherosclerotic plaques and are thought to play an important role in atherogenesis. Dendritic cells express major histocompatibility complex I and II, human leukocyte antigen-DR, CD1a, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and co-stimulatory molecule on their surfaces and this explains their unique ability to activate naive T cells. Factors such as oxidized low-density lipoprotein, hypoxia, nicotine, heat shock proteins, and altered nitric oxide synthase activity of the endothelium, all of which cause endothelial dysfunction, have a significant impact on dendritic cell adherence to endothelium and maturation. Mature dendritic cells are capable of presenting antigens to T cells, and activation of T cells leads to release of cytokines, which play an important role in the progression of disease. Drugs such as statins and diltiazem have been shown to protect endothelial function by inhibition of dendritic cell-endothelial cell interaction, and can be applied to delay the progression of cardiovascular diseases.     

炎性细胞在动脉粥样硬化中作用的研究进展

心血管疾病(CVD)严重威胁人类的健康,动脉粥样硬化(As)作为CVD的重要病理基础,是氧化脂质在血管壁沉积引起的一种慢性免疫炎性病变。各种免疫炎性细胞在As的发生发展中起关键作用,因此不断探索免疫细胞在病变中的作用机制,对研究CVD的治疗策略是至关重要的。本文主要对中性粒细胞、单核细胞、淋巴细胞、树突状细胞、肥大细胞在As中的作用进行综述。     

树突状细胞在动脉粥样硬化中的作用

目前研究认为动脉粥样硬化是一种慢性炎症免疫性疾病.树突状细胞作为功能最强的专职抗原提呈细胞,在动脉粥样硬化中具有重要的作用.成熟的树突状细胞把抗原提呈给T细胞并激活T细胞释放细胞因子参与动脉粥样硬化.现就树突状细胞在动脉粥样硬化中的作用作阐述.     

CD8+ cytotoxic lymphocytes in cutaneous leishmaniasis

OBJECTIVE: Review of the literature on the role of CD8+ T cell in the immune response against Leishmania species that cause cutaneous leishmaniasis. The role of macrophages, dendritic cells, CD4 T cells and NK cells has been extensively analyzed in leishmaniasis, yet very little knowledge has been gained on CD8+ T cells in this disease. Murine models of leishmaniasis suggest that CD8+ T cells participate through IFNg production, yet their cytotoxic capacity may also play a crucial role, as has been found in human disease. It is an enigma what mechanisms underlie the CD8+ T cell activation. It is possible that dendritic cells activate CD8+ T cells through mechanisms that include antigen traspresentation. A better understanding of CD8+ T cells in the immune response against Leishmania will undoubtedly provide new insights into the physiopathogenesis of the disease that could lead to new therapeutic approaches against leishmaniasis.     

Characterization of antigen-presenting dendritic cells in the peripheral blood and colonic mucosa of patients with ulcerative colitis

OBJECTIVE: Increased lymphocyte activation and production of inflammatory cytokines are implicated in the pathogenesis of ulcerative colitis. Because antigen-presenting dendritic cells play a cardinal role in the activation and survival of activated lymphocytes, the aim of the present study was to characterize dendritic cells in ulcerative colitis. DESIGN: This study was designed to compare the phenotypes and functions of peripheral blood dendritic cells among healthy normal volunteers and patients with ulcerative colitis or Crohn's disease. Activated dendritic cells were also localized at the colonic mucosa. METHODS: Peripheral blood dendritic cells were generated from 15 patients with ulcerative colitis, 10 patients with Crohn's disease and 15 healthy control volunteers. The stimulatory capacities of dendritic cells were analysed in an allogenic mixed lymphocyte reaction. Nitric oxide was detected by the Griess method. Single- and dual-colour flow cytometry was employed to study the levels of maturation of dendritic cells. Activated dendritic cells were localized immunohistochemically in the colonic mucosa. RESULTS: In comparison to normal controls, peripheral blood dendritic cells from patients with ulcerative colitis showed significantly increased stimulatory capacities (P < 0.05) and produced significantly higher levels of nitric oxide (P < 0.05). The numbers of activated dendritic cells were also significantly higher in ulcerative colitis (P < 0.05). Mature and activated dendritic cells expressing the CD83 antigen were detected at the inflamed colonic mucosa in patients with ulcerative colitis and Crohn's disease. CONCLUSIONS: Activated and mature dendritic cells may have a role in the induction of an exacerbated immune response in ulcerative colitis. This study provides the scientific and logical basis for blocking the maturation and activation of dendritic cells in ulcerative colitis as a new therapeutic intervention.     

树突状细胞在疟原虫感染免疫中的作用

疟疾分布广泛,危害严重,所引起的并发症在人群中具有很高的死亡率.在疟疾流行区,由于抗药性原虫株的产生和蚊媒的扩散,使疟疾防治难度不断加大.为此,寻找新的抗疟药和研究疟疾疫苗显得尤为迫切.这些研究首先需要对疟原虫与宿主间的相互作用有充分的了解.在疟原虫感染与免疫的研究中,树突状细胞作为宿主对抗疟原虫感染免疫的关键环节,日益受到关注,并成为国内外研究的热点.该文就当前树突状细胞在宿主抗疟原虫感染中作用机制的研究进展作一综述.     

Decreased number of circulating plasmacytoid dendritic cells in patients with atherosclerotic coronary artery disease

BACKGROUND: Dendritic cells are potent antigen-presenting and immune modulating cells that have been implicated in the development of atherosclerosis. In human blood, two distinct lineages are distinguished: plasmacytoid dendritic cells and myeloid dendritic cells. Although dendritic cells have been described in atherosclerotic plaques, no information exists concerning circulating blood dendritic cells in atherosclerosis. This study aims to evaluate the number of circulating dendritic cells in patients with coronary artery disease. The relation with the extent of coronary artery disease, the clinical syndrome and with a marker of inflammation will be documented. METHODS: Patients with angiographically proven coronary artery disease (n=18) and age and sex-matched controls (n=18) were included. Myeloid dendritic cells and plasmacytoid dendritic cells were detected with the specific blood dendritic cell antigens, blood dendritic cell antigen-1 and blood dendritic cell antigen-2, respectively. RESULTS: Absolute and relative numbers of circulating plasmacytoid dendritic cells were significantly lower in patients with coronary artery disease (5722+/-601/ml and 0.08+/-0.01%) than in controls (12,640+/-1289/ml and 0.21+/-0.02%). Plasmacytoid dendritic cells were more decreased in patients with troponin-positive unstable coronary syndromes than in patients with low troponin values, and tended to be lower in more extensive coronary artery disease. Absolute myeloid dendritic cells numbers tended to be reduced in patients, whereas relative numbers were significantly decreased: 11,857+/-1895/ml versus 15,226+/-928/ml and 0.17+/-0.03% versus 0.26+/-0.01% in controls. CONCLUSIONS: The present study shows a significant decrease of circulating blood dendritic cell antigen-2 positive plasmacytoid dendritic cells in patients with coronary artery disease. The decrease tended to be more pronounced in unstable coronary syndromes and extensive coronary artery disease, suggesting a possible role of dendritic cells in plaque progression and rupture.     

Fully competent dendritic cells as inducers of T cell anergy in autoimmunity

Mature immunologically competent dendritic cells are the most efficient antigen-presenting cells that powerfully activate T cells and initiate and sustain immune responses. Indeed, dendritic cells are able to efficiently capture antigens, express high levels of costimulatory molecules, and produce the combination of cytokines required to create a powerful immune response. They are also considered to be important in initiating autoimmune disease by efficiently presenting autoantigens to self-reactive T cells that, in this case, will mount a pathogenic autoimmune reaction. Triggering T cells is not a simple on-off procedure, as T cell receptor responds to minor changes in ligand with gradations of T cell activation and effector functions. These "misfit" peptides have been called Altered Peptide Ligands, and have been shown to have important biological significance. Here, we show that fully capable dendritic cells may present, upon natural antigen processing, a self-epitope with Altered Peptide Ligands features that can unexpectedly induce anergy in a human autoreactive T cell clone. These results indicate that presentation of a self-epitope by immunologically competent dendritic cells does not always mean "danger" and show a mechanism involved in the fine balance between activation and tolerance induction in humans.