DYNAMIC ANALYSIS OF MEMORY T GEELs IN RELAPSE AND CHRONIC PROGRESSION IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS

多发性硬化症发病机制中复发和慢性进展记忆T凝胶的动态分析

基本信息

批准号：
15590875
负责人：
FUJIHARA Kazuo
金额：
$ 2.05万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590875/
关键词：
multiple sclerosis demyelinating disease optic-spinal MS conventional MS memory T cells CCR7 immunological memory antigen presentation

项目摘要

In multiple sclerosis (MS), immunological memories to cause inflammatory demyelination are renewed and retained for long periods, and they are critically important in the lesion development during relapse and chronic progression of the disease. Recent studies demonstrated that the expression of CCR7, a chemokine receptor, is crucial in memory T cell differentiation and the subset identification. Central memory T cells (cmT, CD45RO+CCR7+) have no meaningful effector function, but are resistant to apoptosis and retain immunological memories. On the other hand, effector memory T cells (emT, CD45RO+CCR7-) efficiently migrate to sites of inflammation, secrete inflammatory cytokines, and become apoptotic.In the present study, we analyzed dynamic state of memory T cells in MS.1.A flow cytometric analysis of memory T cell subsets in the cerebrospinal fluid (CSF) and peripheral blood was conducted in MS, viral meningitis and control. The percentages of emT were higher in CSF than in blood in all groups. The cmT subset was significantly increased in MS than in other groups, suggesting its critical role in relapse of MS.2.We immunohistochemically analyzed the expression and distribution of CCR7 and its ligands CCL19 and CCL21 in the cerebral white matter of autopsied brains of MS and controls. CCR7 was stained positive in some dendritic cells, activated macrophages and lymphocytes localized in the periphery of demyelinated lesions and surrounding regions, which suggests on-going antigen presentation. CCL19 was expressed on the venules around the plaques, and that might contribute to the migration of CCR7+ cells to the MS lesions. Messenges of CCR7 and CCL19 were also increased in the regions, supporting the immunohistochemical findings.3.Memory T cell subsets were flow-cytometrically analyzed in the peripheral blood lymphocytes of MS patients stimulated with myelin basic protein twice. As time went by, the emT subset decreased, while the cmT subset increased.

在多发性硬化症（MS）中，导致炎性脱髓鞘的免疫记忆会被更新并长期保留，它们在疾病复发和慢性进展期间的病变发展中至关重要。最近的研究表明，趋化因子受体 CCR7 的表达对于记忆 T 细胞的分化和亚群识别至关重要。中央记忆T细胞（cmT、CD45RO+CCR7+）没有有意义的效应功能，但能抵抗细胞凋亡并保留免疫记忆。另一方面，效应记忆T细胞（emT，CD45RO+CCR7-）有效地迁移到炎症部位，分泌炎症细胞因子，并发生凋亡。在本研究中，我们分析了MS.1中记忆T细胞的动态状态。对 MS、病毒性脑膜炎和对照患者的脑脊液 (CSF) 和外周血中的记忆 T 细胞亚群进行流式细胞术分析。所有组中脑脊液中 emT 的百分比均高于血液中的。 MS组中cmT亚群较其他组显着增加，提示其在MS复发中发挥关键作用。 2.我们采用免疫组化方法分析了MS和MS尸检脑白质中CCR7及其配体CCL19和CCL21的表达和分布。控制。 CCR7 在脱髓鞘病变周围和周围区域的一些树突状细胞、活化的巨噬细胞和淋巴细胞中呈阳性，这表明正在进行的抗原呈递。 CCL19 在斑块周围的小静脉上表达，这可能有助于 CCR7+ 细胞迁移至 MS 病变。这些区域的CCR7和CCL19信号也有所增加，支持了免疫组化的结果。3.流式细胞仪分析了髓磷脂碱性蛋白两次刺激的MS患者外周血淋巴细胞中的记忆T细胞亚群。随着时间的推移，emT子集减少，而cmT子集增加。