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树突状细胞在中枢神经系统免疫介导的炎症性疾病中的潜在作用。

The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system.

作者信息

Matyszak M K, Perry V H

机构信息

University Department of Pharmacology, University of Oxford, U.K.

出版信息

Neuroscience. 1996 Sep;74(2):599-608. doi: 10.1016/0306-4522(96)00160-1.

DOI:10.1016/0306-4522(96)00160-1
PMID:8865208
Abstract

Dendritic cells of the rat were studied immunohistochemically with MRC OX62 monoclonal antibody and using electron microscopy. In normal CNS, a small number of OX62+ cells was detected in the choroid plexus and meninges. These cells were absent from other CNS and peripheral nervous system sites studied. Dendritic cells were also studied in two models of immune-mediated inflammatory conditions in the CNS. These were: acute experimental allergic encephalomyelitis and aberrant delayed-type hypersensitivity lesions induced as a response to heat-killed bacillus Calmette-Guérin sequestrated behind the blood-brain barrier. In addition, a group of animals with a delayed-type hypersensitivity response was treated with dexamethasone to assess the effect of steroid treatment on T-cells and OX62+ cells in CNS lesions. Dendritic cells were present in many but not all lesions in acute experimental allergic encephalomyelitis and their numbers were small. In experimental allergic encephalomyelitis lesions, dendritic cells were found predominantly in perivascular cuffs, where they constituted approximately 2% of the total number of major histocompatibility complex class II+ cells. Some of these cells were also detected in the CNS parenchyma, close to the perivascular cuff. In contrast, dendritic cells were present in all delayed-type hypersensitivity lesions studied. Their number in delayed-type hypersensitivity lesions was significantly higher than in experimental allergic encephalomyelitis lesions. Numerous OX62+ cells were found, even in three-month-old lesions. Electron microscopy studies revealed that these cells were often in close contact with lymphocytes. There was no significant change in the density of OX62+ cells, IL2R+ cells and OX19+ T-cells in delayed-type hypersensitivity lesions after seven-day treatment with dexamethasone, although there was a considerable reduction in the number of CD45RA+ T-cells. The high numbers of dendritic cells found in the delayed-type hypersensitivity lesions may be important in contributing to the chronicity of the response. They may also initiate autoimmune responses to CNS antigens uncovered during bystander tissue damage which occurs as a consequence of aberrant delayed-type hypersensitivity responses.

摘要

采用MRC OX62单克隆抗体并利用电子显微镜对大鼠树突状细胞进行了免疫组织化学研究。在正常中枢神经系统中,脉络丛和脑膜中检测到少量OX62+细胞。在研究的其他中枢神经系统和周围神经系统部位未发现这些细胞。还在中枢神经系统免疫介导的炎症性疾病的两种模型中研究了树突状细胞。这两种模型分别是:急性实验性过敏性脑脊髓炎和因血脑屏障后隔离的热灭活卡介苗引发的异常迟发型超敏反应病变。此外,对一组具有迟发型超敏反应的动物用 dexamethasone进行治疗,以评估类固醇治疗对中枢神经系统病变中T细胞和OX62+细胞的影响。在急性实验性过敏性脑脊髓炎的许多但并非所有病变中都存在树突状细胞,且数量较少。在实验性过敏性脑脊髓炎病变中,树突状细胞主要存在于血管周围套中,在主要组织相容性复合体II类+细胞总数中约占2%。在中枢神经系统实质中靠近血管周围套的部位也检测到了其中一些细胞。相比之下,在所研究的所有迟发型超敏反应病变中都存在树突状细胞。它们在迟发型超敏反应病变中的数量明显高于实验性过敏性脑脊髓炎病变。即使在三个月大的病变中也发现了大量OX62+细胞。电子显微镜研究显示,这些细胞常与淋巴细胞紧密接触。用dexamethasone治疗七天后,迟发型超敏反应病变中OX62+细胞、IL2R+细胞和OX19+ T细胞的密度没有显著变化,尽管CD45RA+ T细胞数量有相当程度的减少。在迟发型超敏反应病变中发现的大量树突状细胞可能对反应的慢性化起重要作用。它们也可能引发对旁观者组织损伤过程中暴露的中枢神经系统抗原的自身免疫反应,这种组织损伤是由异常迟发型超敏反应导致的。

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