Immunopathogenesis of Multiple Sclerosis

多发性硬化症的免疫发病机制

• 批准号: 7052790
• 负责人: MICHAEL K RACKE
• 金额: $ 1.74万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052790
• 关键词: B lymphocyte; T lymphocyte; cerebrospinal fluid; clinical research; disease /disorder etiology; human subject; immunopathology; immunosuppression; leukocyte activation /transformation; mitoxantrone; multiple sclerosis; myelinopathy; nerve /myelin protein; pathologic process; patient oriented research; role model

DESCRIPTION (provided by applicant): The studies which are outlined in this proposal represent a very exciting and ambitious plan to address the issues of the magnitude, fine specificity, and precise nature of the autoreactive T cell response in MS and further explore the potential contribution of clonally expanded CSF B cells to disease pathogenesis. Using highly innovative approaches we plan to characterize these responses at a single cell level and analyze the TCR usage and CSF B cell repertoire, specifically in the context of various therapeutic interventions. These studies will determine the effectiveness of immune reconstitution with respect to the response to myelin antigens and compare that with what happens to the immune response following more standard immune suppression using mitoxantrone. We will also be able to compare this information with the data we are generating on patients with RRMS receiving more standard immunomodulatory therapies. We anticipate that these studies will provide important information with regard to the immunopathogenesis of MS. Data from these studies will allow the PI to design clinical trials testing novel therapeutic agents for MS based on the translational studies. In addition, the proposed Award will allow the PI to concentrate his efforts on mentoring the next generation of clinician scientists focusing their efforts on multiple sclerosis.

描述（由申请方提供）：本提案中概述的研究代表了一项非常令人兴奋和雄心勃勃的计划，旨在解决MS中自身反应性T细胞应答的幅度、精细特异性和精确性质的问题，并进一步探索克隆扩增的CSF B细胞对疾病发病机制的潜在贡献。使用高度创新的方法，我们计划在单细胞水平上表征这些反应，并分析TCR使用和CSF B细胞库，特别是在各种治疗干预的背景下。这些研究将确定免疫重建对髓鞘抗原的反应的有效性，并将其与使用米托蒽醌进行更标准的免疫抑制后的免疫反应进行比较。我们还将能够将这些信息与我们正在生成的接受更标准免疫调节治疗的RRMS患者的数据进行比较。我们预计这些研究将提供关于MS免疫发病机制的重要信息。这些研究的数据将允许PI基于转化研究设计检测MS新型治疗药物的临床试验。此外，拟议的奖项将允许PI集中精力指导下一代临床科学家专注于多发性硬化症的努力。