滤泡调节性T细胞（TFR）是一类新发现的专职调节生发中心免疫反应的CXCR5+Foxp3+双阳性CD4+T细胞亚群，在维持机体免疫耐受中发挥重要作用，其在重症肌无力（MG）中的作用及机制尚不明确。本课题组前期研究发现：MG患者外周血中TFR细胞频率明显低于健康人群，全身型MG患者的TFR细胞较单纯眼肌型亦明显减少。本项目拟在既往工作基础上，进一步检测MG患者和EAMG小鼠TFR细胞的表型和特性，探讨TFR细胞在MG疾病发生中的作用及其与病情特点的相关性；同时应用单链抗体scFvFoxp3-9R负载Blimp-1 siRNA治疗EAMG小鼠，检测AChR特异性T、B细胞的免疫反应，揭示TFR细胞在MG中的免疫调节机制。单链抗体介导的RNAi技术具有高效、靶向性及低免疫原性的优势，应用这一技术促进TFR细胞克隆扩增的免疫治疗策略，将为MG乃至人类自身免疫性疾病的治疗提供新的思路。

Follicular regulatory T cells (TFR) are recently defined CD4+T cell subsets with CXCR5+Foxp3+ phenotype, which locate in the germinal centers to regulate the immune response and play an important role in maintaining immune tolerance. Less is known about TFR cells in the pathogenesis of MG. Our preliminary study had found that the frequency of TFR cells in MG patients is significantly lower than that in healthy controls,and decreased TFR cells in generalized MG compared to ocular MG. On this project,We'll confirm the immunologic characteristics of TFR cells in MG patients and EAMG mice, to explore the funcation of TFR cells in the progression of MG. Meanwhile, scFvFoxp3-9R fusing with Blimp-1 siRNA will be constructed and administered to EAMG mice. By detecting the AChR specific T and B cells response and key components in signaling pathway,the up-regulating of TFR cells and restoration of immune tolerance will be evaluated and the potential role of TFR cells in the pathogenesis of MG will be declared. The immunotherapeutic strategy based on the single-chain antibody-mediated RNAi technology will bring up a new world for treating MG even other autoimmune diseases, with the advantage of high efficiency,specific targeting and low immunogenicity.