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

• 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

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，引起炎性脱髓鞘的免疫记忆被更新并长期保留，在疾病复发和慢性进展过程中，它们在病变的发展中至关重要。最近的研究表明，趋化因子受体CCR7的表达在记忆T细胞分化和亚群识别中起着至关重要的作用。中枢记忆T细胞(CMT，CD45RO+CCR7+)没有明显的效应功能，但具有抗凋亡和保留免疫记忆的功能。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，并成为凋亡细胞。在本研究中，我们分析了MS患者记忆T细胞的动态变化。1.对MS、病毒性脑膜炎和对照组的脑脊液和外周血中的记忆T细胞亚群进行了流式细胞术分析。各组脑脊液中EMT的百分比均高于血液中EMT的百分比。2.免疫组织化学方法检测CCR7及其配体CCL19和CCL21在MS和对照组脑白质中的表达和分布。CCR7在部分树突状细胞、活化的巨噬细胞和位于脱髓鞘病变周边及周围区域的淋巴细胞中呈阳性表达，提示正在进行抗原递呈。CCL19表达于斑块周围的小静脉上，可能参与了CCR7+细胞向MS病变的迁移。髓鞘碱性蛋白刺激的MS患者外周血中的记忆T细胞亚群进行了流式细胞术分析。随着时间的推移，EMT亚集减少，而CMT亚集增加。

项目成果

多発性硬化症の治療の進め方 対症療法とケアの進め方・生活指導の進め方

如何进行多发性硬化症的治疗 如何进行对症治疗和护理/如何进行生活方式指导

• 发表时间: 2004
• 期刊: Modern Physician 24
• 作者: Kawanokuchi;J.;Mizuno;T.;Kato;H.;Mitsuma;N.;Suzumura;A.;藤原一男
• 通讯作者: 藤原一男

Devic病(neuromyelitis optica)

Devic 病（视神经脊髓炎）

• 发表时间: 2004
• 期刊: Modern Physician 24
• 作者: Misu T;Hashimoto Y. et al.;藤原一男;中島一郎;Hashimoto Y. et al.;藤原一男;宮澤イザベル
• 通讯作者: 宮澤イザベル

Soluble CD26 and CD30 levels in CSF and sera of patients with relapsing neuromyelitis optica.

复发性视神经脊髓炎患者脑脊液和血清中可溶性 CD26 和 CD30 水平。

• 期刊: J Neurol (in press)
• 作者: Misu T;小野寺淳一;Nakashima I.;Lennon VA.;Nakamura M.;Nakashima I.;Nakashima I.;Narikawa K;Matsumoto Y;藤原一男;三須建郎;Nakashima I;藤原一男;斎田孝彦;Fujihara K.;Misu T.;Saida T.;Nakashima I.;Narikawa K;Narikawa K.
• 通讯作者: Narikawa K.

Therapeutic guidelines of neuroimmunological diseases.

神经免疫疾病治疗指南。

• 发表时间: 2004
• 作者: Misu T;小野寺淳一;Nakashima I.;Lennon VA.;Nakamura M.;Nakashima I.;Nakashima I.;Narikawa K;Matsumoto Y;藤原一男;三須建郎;Nakashima I;藤原一男;斎田孝彦;Fujihara K.;Misu T.;Saida T.;Nakashima I.;Narikawa K;Narikawa K.;Takahashi T.;斎田孝彦;Saida T.
• 通讯作者: Saida T.

藤原一男: "多発性硬化症のインターフェロンβ療法"Current Insights in Neurological Science. 11. 5-5 (2003)

Kazuo Fujiwara：“干扰素β疗法治疗多发性硬化症”《神经科学最新见解》11. 5-5 (2003)。