多发性肌炎（polymyositis,PM）是一种以CD8+T细胞介导的严重自身免疫病，病程可迁延至数年。目前已经明确协同刺激分子在PM发病中起重要作用，但关键分子及机制尚不清楚。国外研究发现OX40通过PKC介导的NF-κB激活在T细胞增殖及维持存活中起重要作用；我们前期研究发现在PM患者中有OX40+CD8+T细胞增多，肌细胞上OX40L强阳性表达；因此推测PM中OX40/PKC/NF-κB途径对CD8+T细胞的增殖、存活及对肌细胞毒性作用起重要调节作用。本项目通过对T细胞功能测定、PM患者肌组织协同刺激信号转导相关分子的检测、PM小鼠模型的各项功能研究以及抗体阻断干预实验，从细胞、组织、动物水平来研究PM中OX40/PKC/NF-κB途径对CD8+T细胞维持肌细胞毒性的调节作用及其机制，为将来PM的新诊断标记及新治疗策略打下理论基础。

Polymyositis is a CD8+ T cell-mediated serious autoimmune disease. It could be persistent to several years. Nowadays, we know the costimulatory molecules play an very important role in PM, but which is the key is remains unclear. Researches abroad have found that OX40 induced PKC-mediated NF-κB activation plays an important role in the proliferation and maintenance of survival of T cell. We have found that there are increasing of OX40+CD8+ T cell in PM, OX40L are strong positive. We believe that the OX40/PKC/NF-κB pathway plays an very important role in the proliferation and maintenance of survival of CD8+ T cell in PM. To expound the role of OX40/PKC/NF-κB pathway in the proliferation and maintenance of survival of CD8+ T cell in PM, this research will develop T cells and related signal transduction molecules of PM, T cell function in vitro and animal experiments. Establish the theoretical foundation for the new diagnostic markers and new therapeutic strategies of PM in the future.