ANALYSIS OF IN VIVO HPRT MUTANT T CELLS IN MS

MS 体内 HPRT 突变 T 细胞分析

• 批准号: 3413799
• 负责人: SUBRAMANIAM SRIRAM
• 金额: $ 13.51万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413799
• 关键词: T cell receptor; T lymphocyte; cellular pathology; clone cells; flow cytometry; gene expression; gene frequency; gene mutation; human genetic material tag; human subject; hypoxanthine phosphoribosyltransferase; interferons; interleukin 2; interleukin 3; interleukin 4; longitudinal human study; multiple sclerosis; myelin basic proteins; myelin proteolipid; pathologic process; polymerase chain reaction; protein biosynthesis; protein purification; surface antigens; tissue /cell culture; tobacco; tumor necrosis factor alpha; tumor necrosis factor beta

Multiple sclerosis (MS) is considered to be a T cell mediated autoimmune disease, although the nature of the autoantigen has remained elusive. We propose that in auto e disease including MS, there is an unchecked amplification of T cells in vivo. These cells are dividing and therefore selectively enriched by the hprt mutant clonal assay. This assay will provide a method to identify and study T cells that are representative of clones dividing in vivo. Our preliminary data has shown that the hprt mutant frequency is increased in a number of autoimmune diseases, including MS. Furthermore, five or six MS patients have hprt mutant T cells that show reactivity to myelin basic protein while wild type clones do not. Our overall objective is to study the mutant frequency in patients over time, and determine the extent of this antigen reactivity in the MS population, and define the fine specificity and T cell receptor gene usage in these clones.

多发性硬化症（MS）被认为是T细胞介导的 自身免疫性疾病，尽管自身抗原的性质仍然存在 难以捉摸。 我们认为，在包括MS在内的汽车疾病中， T细胞在体内未经检查的扩增。 这些细胞正在分裂， 因此通过HPRT突变体克隆测定选择性富集。 该测定 将提供一种方法来识别和研究具有代表性的T细胞 克隆体在体内分裂。 我们的初步数据显示， 突变频率在许多自身免疫性疾病中增加，包括 女士 此外，5或6名MS患者具有hprt突变T细胞， 显示出对髓鞘碱性蛋白反应性，而野生型克隆没有。 我们的总体目标是研究患者的突变频率 并确定MS中该抗原反应性的程度 群体，并定义精细特异性和T细胞受体基因使用 在这些克隆中。