Granzyme B + CD8 + T cells with terminal differentiated effector signature determine multiple sclerosis progression

作者：Ziyan Shi, Xiaofei Wang, Jiancheng Wang, Hongxi Chen, Qin Du, Yanlin Lang, Lingyao Kong, Wenqin Luo, Yuhan Qiu, Ying Zhang, Chen Li, Dingke Wen, Jie Yao, Xia Cheng, Linjun Cai, Xue Lin, Rui Wang, Zichao Mou, Shuangjie Li, Duanya Liu, Hong Zhou, Hongyu Zhou, Hongyu Zhou, Hongyu Zhou, Mu Yang · 发表于：Journal of Neuroinflammation · 年份：2023 · DOI：10.1186/s12974-023-02810-0 · 被引用次数：31 · 研究领域：Multiple Sclerosis Research Studies、Neuroinflammation and Neurodegeneration Mechanisms、T-cell and B-cell Immunology

Abstract Background Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing–remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS. Methods Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively. Results Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed...