MECHANISMS OF CELLULAR IMMUNE REACTIONS IN THE CNS

中枢神经系统细胞免疫反应的机制

• 批准号: 2393097
• 负责人: RAYMOND A SOBEL
• 金额: $ 18.26万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2393097
• 关键词: T cell receptor; antigen presentation; cellular immunity; central nervous system; experimental allergic encephalomyelitis; fibronectins; histopathology; human tissue; immunocytochemistry; immunoelectron microscopy; inflammation; integrins; laboratory mouse; laboratory rat; laminin; monoclonal antibody; multiple sclerosis; myelin proteolipid; myelinopathy; neuroimmunomodulation; receptor expression; stress proteins; vitronectin

The long range goal of this project is to understand mechanisms of cellular immune reactions in the central nervous system (CNS). The overall hypothesis is that surface expression of specific molecules on inflammatory and CNS resident cells play critical roles in immune- mediated injury. CNS tissue samples from animals with experimental allergic encephalomyelitis (EAE), a model of multiple sclerosis (MS), and from patients with CNS diseases are studied using routine histology and immunohistochemistry at the light microscopic and ultrastructural levels to visualize directly the locations of cell surface molecules that are effectors and targets in CNS immune reactions. The studies to be performed in the proposed grant period will determine: 1. (A) The regions of myelin proteolipid protein (PLP) that are localized on the external surface (intermediate dense line) and those epitopes that are localized on the cytoplasmic face (major dense line) in compact CNS myelin and (B) whether antibodies with specificities to epitopes on the external surface induce more demyelination than antibodies to epitopes on the cytoplasmic face in vivo in an acute EAE model. 2. Whether cell-surface integrin receptors of vitronectin and laminin are expressed on inflammatory cells in lesions of EAE and MS and whether this expression and colocalization with vitronectin and laminin correlate with the degree of inflammation and demyelination. 3. Whether the temporal dynamics, extent of infiltration of T cell receptor V tau delta+ cells and their target heat shock proteins correlate with clinical manifestations and type and degree of histologic injury in a mouse model of chronic EAE. This research addresses both the normal molecular structure of CNS myelin and mechanisms of demyelination in MS and other demyelinating diseases. Because integrins are both used by neoplastic cells for tissue invasion and by microorganisms as receptors, the results will also have implications for the pathogenesis of CNS metastatic tumors and infections.

该项目的远距离目标是了解 中枢神经系统（CNS）中的细胞免疫反应。 这 总体假设是特定分子在上面的表面表达 炎症和中枢神经系统驻留细胞在免疫中起关键作用 介导的伤害。 来自动物的中枢神经系统组织样品 过敏性脑脊髓炎（EAE），多发性硬化症模型（MS）和 使用常规组织学和 光学和超微结构水平的免疫组织化学 直接可视化细胞表面分子的位置 中枢神经系统免疫反应的效应子和靶标。 研究是 在拟议的赠款期间进行的将确定： 1。（a）髓磷脂蛋白蛋白蛋白（PLP）的区域 位于外表面（中间密集线）和 位于细胞质面（主要密集线）的表位 在紧凑的CNS髓磷脂中，（b）具有特异性的抗体是否 外表面上的表位诱导的脱髓鞘比 急性EAE中体内细胞质面部表位的抗体 模型。 2。是否是细胞表面整合蛋白受体的玻霉素和层粘连蛋白的受体 在EAE和MS病变中的炎症细胞上表达 这种表达和与玻璃体蛋白和层粘连蛋白的共定位相关 具有炎症和脱髓鞘的程度。 3。时间动力学，T细胞的浸润程度是否 受体v tau delta+细胞及其目标热激蛋白 与临床表现以及组织学的类型和程度相关 慢性EAE小鼠模型的损伤。 这项研究既解决CNS髓磷脂的正常分子结构 MS和其他脱髓鞘疾病中脱髓鞘的机制。 因为肿瘤细胞都将整联蛋白用于组织侵袭 通过微生物作为受体，结果也将具有 对中枢神经系统转移性肿瘤的发病机理的意义 感染。

项目成果

Implantation of human meningiomas into the subrenal capsule of the nude mouse. A model for studies of tumor growth.

将人脑膜瘤植入裸鼠肾下囊。

• DOI: 10.3171/jns.1989.71.4.0545
• 发表时间: 1989
• 期刊: Journal of neurosurgery
• 影响因子: 4.1
• 作者: Medhkour,A;VanRoey,M;Sobel,RA;Fingert,HJ;Lee,J;Martuza,RL
• 通讯作者: Martuza,RL

Fibronectin in multiple sclerosis lesions.

多发性硬化症病变中的纤连蛋白。

• 发表时间: 1989
• 期刊: The American journal of pathology
• 作者: Sobel,RA;Mitchell,ME
• 通讯作者: Mitchell,ME

A model of coccidioidal meningoencephalitis and cerebrospinal vasculitis in the rabbit.

兔球孢子菌脑膜脑炎和脑脊髓血管炎模型。

• DOI: 10.1086/515689
• 发表时间: 1998
• 期刊: The Journal of infectious diseases
• 作者: Williams,PL;Sobel,RA;Sorensen,KN;Clemons,KV;Shuer,LM;Royaltey,SS;Yao,Y;Pappagianis,D;Lutz,JE;Reed,C;River,ME;Lee,BC;Bhatti,SU;Stevens,DA
• 通讯作者: Stevens,DA

Vitronectin and integrin vitronectin receptor localization in multiple sclerosis lesions.

玻连蛋白和整合素玻连蛋白受体在多发性硬化症病变中的定位。

• DOI: 10.1097/00005072-199503000-00007
• 发表时间: 1995
• 期刊: Journal of neuropathology and experimental neurology
• 影响因子: 3.2
• 作者: Sobel,RA;Chen,M;Maeda,A;Hinojoza,JR
• 通讯作者: Hinojoza,JR

Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis in a cross between SJL/J and B10.S mice.

SJL/J 和 B10.S 小鼠杂交实验性自身免疫性脑脊髓炎易感性的遗传分析。

• 发表时间: 1996
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Encinas,JA;Lees,MB;Sobel,RA;Symonowicz,C;Greer,JM;Shovlin,CL;Weiner,HL;Seidman,CE;Seidman,JG;Kuchroo,VK
• 通讯作者: Kuchroo,VK