Autoaggressive CD8 T cells in polymyositis

多发性肌炎中的自身攻击性 CD8 T 细胞

基本信息

批准号：
13670452
负责人：
KOHSAKA Hitoshi
金额：
$ 0.9万
依托单位：
Tokyo Medical & Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670452/
关键词：
polymiositis CD8T cells autoimmunity

项目摘要

Polymyositis (PM) involves destruction of striated muscles by autoaggressive CD8 T cells, which accumulate and secrete cytotoxic effecter molecules in the affected muscles. On the other hand, studies of peripheral T cell repertoires from normal individuals and patients with viral infections have shown that primed CD8 T cells, unlike CD4 T cells are prone to expand clonally and persist as large populations in the peripheral blood. This made us assume that autoaggressive myocytotoxic CD8 T cells would be expanded clonally in the peripheral blood from patients with PM. By clonal analyzes of peripheral T cells from patients and age-matched controls, we show here that clonal expansion of CD8 T cells, but not that of CD4 T cells, was significantly more frequent in patients. In analogy to virus-specific T cells, the expanded T cells persisted as large populations over time. Analysis of the muscle biopsy specimens revealed that some of the expanded clones were infiltrating in the affected muscles from the same patients. These results provide the first evidence that local autoimmune reaction directly elicits significant biases in peripheral T cell repertoire. Since the expanded cells, which should be candidate autoaggressive T cells, are readily isolated from peripheral blood, our findings should give us an immediate clue to analysis of the pathogenic T cells in PM.Following studies failed to show that the expanded cells recognize human C-protein that is responsible for a rodent model of PM. The future studies will be focused on the antigen specificity of the expanded cells.

多聚肌炎（PM）涉及自动攻击CD8 T细胞破坏横纹肌肉，后者积累并分泌受影响的肌肉中的细胞毒性效应子分子。另一方面，对正常个体和病毒感染患者的外周T细胞谱系的研究表明，与CD4 T细胞不同，CD4 T细胞很容易在外围血液中延伸并持续存在，并且在外周血中持续存在。这使我们假设自身攻击性肌细胞毒性CD8 T细胞将在PM患者的外周血中克隆膨胀。通过对患者和年龄匹配的对照组的外周T细胞的克隆分析，我们在这里表明，患者的CD8 T细胞的克隆膨胀（而不是CD4 T细胞的克隆膨胀）明显更常见。与病毒特异性T细胞类似，随着时间的流逝，扩张的T细胞持续存在。对肌肉活检标本的分析表明，某些扩展的克隆正在来自同一患者受影响的肌肉中。这些结果提供了第一个证据，表明局部自身免疫反应直接引起周围T细胞库中的显着偏见。由于扩展的细胞（应为候选自身攻击性T细胞）很容易从外围血液中分离出来，因此我们的发现应为我们立即提供对PM中病原T细胞的分析的线索。遵循的研究未能表明，扩展的细胞识别负责pM pM的人类C蛋白。未来的研究将集中于扩展细胞的抗原特异性。