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.

这个项目的长期目标是了解 中枢神经系统的细胞免疫反应。这个 总体假设是特定分子在表面的表达 炎性细胞和中枢神经系统驻留细胞在免疫- 居间伤害。实验动物的中枢神经系统组织样本 变态反应性脑脊髓炎(EAE)，多发性硬化症(MS)的模型，以及 用常规组织学和组织学方法对中枢神经系统疾病患者的 光镜和超微结构水平的免疫组织化学 要直接可视化细胞表面分子的位置， 中枢神经系统免疫反应中的效应物和靶点。将进行的研究 在建议的授权期内完成的工作将决定： 1.(A)髓鞘蛋白脂蛋白(PLP)的 定位于外表面(中等密度线)和那些 定位于细胞质表面的表位(主要致密线) 在致密的中枢神经系统髓鞘和(B)是否具有特异性的抗体 表位在外表面引起更多的脱髓鞘 急性EAE患者体内细胞质表面抗原表位的抗体 模特。 2.细胞表面整合素受体是否为玻璃连素和层粘连蛋白 在EAE和MS皮损的炎性细胞上表达，以及 这种表达与玻璃连结蛋白和层粘连蛋白的共定位相关 炎症和脱髓鞘的程度。 3.T细胞的时间动态、浸润程度 受体V tau Delta+细胞及其靶向热休克蛋白 与临床表现及组织学类型和程度相关 慢性EAE小鼠模型的损伤。 本研究对中枢神经系统髓鞘的正常分子结构进行了研究 以及MS和其他脱髓鞘疾病的脱髓鞘机制。 因为整合素都被肿瘤细胞用于组织侵袭 而通过微生物作为受体，结果也将 中枢神经系统转移瘤发病机制的研究进展 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

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

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