Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson’s disease
Pingping Wang, Lifen Yao, Meng Luo, Wenyang Zhou, Xiyun Jin, Zhaochun Xu, Yan Shi, Yiqun Li, Chang Xu, Rui Cheng, Yan Huang, Xiaoyu Lin, Kexin Ma, Huimin Cao, Hongxin Liu, Guangfu Xue, Fang Han, Huan Nie, Qinghua Jiang
Abstract
Abstract Given the chronic inflammatory nature of Parkinson’s disease (PD), T cell immunity may be important for disease onset. Here, we performed single-cell transcriptome and TCR sequencing, and conducted integrative analyses to decode composition, function and lineage relationship of T cells in the blood and cerebrospinal fluid of PD. Combined expression and TCR-based lineage tracking, we discovered a large population of CD8 + T cells showing continuous progression from central memory to terminal effector T cells in PD patients. Additionally, we identified a group of cytotoxic CD4 + T cells (CD4 CTLs) remarkably expanded in PD patients, which derived from Th1 cells by TCR-based fate decision. Finally, we screened putative TCR–antigen pairs that existed in both blood and cerebrospinal fluid of PD patients to provide potential evidence for peripheral T cells to participate in neuronal degeneration. Our study provides valuable insights and rich resources for understanding the adaptive immune response in PD.