Functional profile of activated dendritic cells in unstable atherosclerotic plaque
Functional profile of activated dendritic cells in unstable atherosclerotic plaque
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DOI：
10.1007/s00395-006-0636-x
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发表时间：
2007-03-01
影响因子：
9.5
通讯作者：
Weyand, Cornelia M.
中科院分区：
文献类型：
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作者：
Erbel, Christian;Sato, Kayoko;Weyand, Cornelia M.
背景：不稳定的动脉粥样硬化斑块通常包含活化的巨噬细胞和活化的T细胞浸润。本研究建立了斑块驻留树突状细胞（DC）的功能谱，以检查它们是否可以作为ag呈递细胞促进原位t细胞活化。方法对行颈动脉内膜切除术的无症状患者19例和有症状患者38例进行颈动脉斑块组织采集。从致死性心肌梗死患者中采集正常冠状动脉壁、稳定未破裂斑块和侵蚀不稳定斑块的匹配样本。采用定量PCR和免疫组织化学分析组织中DC活化标志物（CD83、CD86、CCL19、CCL21），并将其与t细胞活化标志物（ifn - γ、tnf - α）进行关联。结果与无症状患者相比，缺血性症状患者颈动脉斑块的特征是存在大量t细胞（P < 0.01）和组织产生高水平的t细胞细胞因子ifn - γ。（P = 0.001）和tnf - α (P = 0.006)。缺血性并发症患者的斑块组织中CD83 （DC激活的标志）和DC趋化因子CCL19 （P = 0.001）和CCL21 （P < 0.02）水平升高。与症状患者的颈动脉斑块相比，不稳定冠状动脉斑块与T细胞积累（P= 0.001）和T细胞趋化因子ifn - γ (P= 0.001)和tnf - α (P= 0.002)的产生相似。免疫组织化学证实CD83(+) DC存在于不稳定斑块的肩部区域，在那里它们产生T细胞吸引趋化因子CCL19和CCL21。活化DC的定位表明成熟DC与表达活化标记CD40配体（CD40L）的T细胞之间存在密切联系。结论激活的和完全成熟的DC在不稳定颈动脉和冠状动脉粥样硬化的炎症浸润特征中具有代表性。这些DC产生趋化因子，从而可以调节细胞进入病变的运输。斑块驻留DC通过表达共刺激配体CD86增强T细胞刺激，为T淋巴细胞提供最佳刺激条件，类似于有组织淋巴组织中的微环境。
Background Unstable atherosclerotic plaque typically contains an infiltrate of activated macrophages and activated T cells. This study established a functional profile of plaque-residing dendritic cells ( DC) to examine whether they can function as Ag-presenting cells to facilitate in situ T-cell activation. Methods Carotid artery plaque tissues were collected from 19 asymptomatic and 38 symptomatic patients undergoing endarterectomy. Matched samples of normal coronary artery wall, stable nonruptured plaque, and eroded unstable plaque were harvested from patients with fatal myocardial infarction. Quantitative PCR and immunohistochemistry were used to analyze the tissues for markers of DC activation (CD83, CD86, CCL19, CCL21) and correlate them with T-cell activation (IFN-gamma, TNF-alpha). Results Carotid artery plaques from patients with ischemic symptoms compared to asymptomatic patients were characterized by the presence of high amount of T-cells (P < 0.01) and tissue production of high levels of the T-cell cytokines IFN-gamma. ( P= 0.001) and TNF-alpha (P = 0.006). Plaque tissues from patients with ischemic complications contained elevated levels of CD83 (P < 0.001), a marker of DC activation, and the DC chemokines CCL19 (P = 0.001) and CCL21 ( P < 0.02).Unstable coronary artery plaques were similarly correlated compared to carotid plaques from symptomatic patients with the accumulation of T cells (P= 0.001) and the production of T cell chemokines IFN-gamma ( P= 0.001) and TNF-alpha (P = 0.002).Immunohistochemistry confirmed the presence of CD83(+) DC in the shoulder region of unstable plaques, where they produced the T cell-attracting chemokines CCL19 and CCL21. Mapping of activated DC demonstrated close contact between mature DC and T cells expressing the activation marker CD40 ligand (CD40L). Conclusion Activated and fully mature DC are represented in the inflammatory infiltrate characteristic for unstable carotid and coronary atheroma. Such DC produce chemokines, and thus can regulate the cell traffic into the lesion. Through the expression of the costimulatory ligand CD86, plaque-residing DC can augment T-cell stimulation and provide optimal stimulation conditions for T lymphocytes, resembling the microenvironment in organized lymphoid tissues.