IMMUNE FUNCTION IN ALLERGIC ENCEPHALOMYELITIS

过敏性脑脊髓炎的免疫功能

• 批准号: 6169639
• 负责人: ROBERT B FRITZ
• 金额: $ 24.65万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6169639
• 关键词: T cell receptor; T lymphocyte; autoimmunity; cell population study; cellular immunity; experimental allergic encephalomyelitis; gene mutation; genetically modified animals; laboratory mouse; tissue /cell culture

The experimentally-induced autoimmune disease, experimental allergic encephalomyelitis (EAE), is the consequence of an inflammatory process initiated by the interaction of neuroantigen-specific T cells with antigenic peptides presented by MHC class II+ antigen presenting cells (APC) in the CNS. The dynamics of the CNS T cell population during acute and relapsing EAE is an important aspect of this disease particularly with respect to the design of immunotherapeutic protocols. An important issue is the mechanism by which the encephalitogenic activity of neuroantigen-specific T cells is regulated in the normal animal as well as during the course of chronic relapsing EAE. We have found that normal regulatory activity is absent in TCR beta-chain knockout (alpha/betaTCR-/-) mice. Preliminary characterization of the regulatory cell population in wild-type mice indicates that the phenotype of the regulatory cell is CD4- CD8-NK1.1+alpha/betaTCR+ or CD4-CD8+NK1.1+alpha/betaTCR+. The hypothesis to be tested is that one or both of these phenotypes is responsible for down-regulation of EAE effector T cells. To test this hypothesis the following Specific Aims are proposed, 1) to assess the role of NK1.1+ alpha/beta+ T cells in recovery from passive EAE using B6 mice with targeted mutations of the immune system, 2) to assess the role of NK1.1+ alpha/beta+ T cells in regulation of self-reactive T cells in the normal individual using B6 mice with targeted mutations of the immune system, 3) to investigate the mechanism of regulation of self-reactive T cells by NK1.1+ alpha/beta+ T cells, 4) to analyze heterogeneity of the a and P-chain CDR3 regions of NK1.1+ alpha/beta+ T cells by spectratypic analysis and nucleotide sequence, and 5) to analyze the interaction of NK1.1+ alpha/beta+ T cells with self-reactive T cells.

实验诱导的自身免疫性疾病，实验性过敏性脑脊髓炎（EAE）是由CNS中MHC II类II+抗原呈现细胞（APC）与神经抗原特异性T细胞与抗原肽相互作用引发的炎症过程的结果。 急性和复发性EAE期间，CNS T细胞群的动力学是该疾病的重要方面，尤其是在免疫治疗方案的设计方面。 一个重要的问题是一种机制，在正常动物以及慢性复发的EAE过程中调节神经抗原特异性T细胞的脑生成活性。 我们发现，在TCRβ链敲除（alpha/betatcr - / - ）小鼠中不存在正常调节活性。 野生型小鼠调节细胞种群的初步表征表明调节细胞的表型为CD4-CD8-NK1.1+alpha/betatcr+或CD4-CD8+NK1.1+alpha/betatcr+。 要检验的假设是，这两个表型中的一种或两个是造成EAE效应T细胞下调的原因。 为了检验该假设，提出了以下特定目的，1）评估NK1.1+α/β+ T细胞在使用具有免疫系统的靶向突变的B6小鼠中的NK1.1+ alpha/beta+ T细胞中的作用，2）评估NK1.1.1.1.1+ Alpha/beta+ T细胞在使用BUCANE中的kinune proune nk1.1.1.1.1.1.1.1.1.1.1.1.1.1.1.1.1+ alpha/beta+ t细胞的作用。 NK1.1+α/β+ T细胞调节自反应T细胞的机制，分析NK1.1+ alpha/beta+ T细胞的A和P链CDR3区的异质性通过频谱分析和核苷酸序列和5个单元格与NK1.1.1.1.1.1.1+ Alpha的相互作用。