Li Wenjie, Chen Sheng, Luo Yuan, Xia Yezi, Ma Qianqian, Yao Qi, Wu Jianqing
Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
Department of Geriatrics, Ningbo First Hospital, Ningbo, Zheijiang 315000, P.R. China.
Exp Ther Med. 2020 Aug;20(2):1021-1029. doi: 10.3892/etm.2020.8758. Epub 2020 May 15.
Parkinson's disease (PD) is a chronic progressive disease that affects the central nervous system with a variety of symptoms. Although the precise etiology of PD is not yet fully understood, there is evidence to suggest that T cells serve an important role in the pathogenesis of PD. However, how T cells are recruited in the brain tissue remains to be elucidated. The present study utilized human samples from patients with and without PD to investigate the infiltration of T cells in lesions in the central nervous system. A chemically-induced mouse PD model was also used to investigate the roles of T cells in the pathogenesis of PD. Depletion of CD4 or CD8 T cells was achieved using neutralizing antibodies. Adhesion molecule levels were assessed by flow cytometry. The results of the study indicated that T cell infiltration was evident in both human and murine samples of PD. Blocking CD4 or CD8 T cells attenuated the severity of murine PD. Intercellular adhesion molecule 1 (ICAM1 or CD54) was upregulated in mouse PD compared with controls, and its receptor, lymphocyte function-associated antigen-1 (LFA1) was overexpressed in T cells of the brain in PD mice compared with controls. Furthermore, inhibition of ICAM1 or LFA1 attenuated PD-associated characteristics in mice. In conclusion, the interaction between ICAM1 and LFA1 plays a role in recruiting T cells to the central nervous system to mediate experimental PD.
帕金森病（PD）是一种影响中枢神经系统的慢性进行性疾病，具有多种症状。尽管PD的确切病因尚未完全明确，但有证据表明T细胞在PD的发病机制中起重要作用。然而，T细胞如何被招募到脑组织中仍有待阐明。本研究利用来自PD患者和非PD患者的人类样本，调查中枢神经系统病变中T细胞的浸润情况。还使用化学诱导的小鼠PD模型来研究T细胞在PD发病机制中的作用。使用中和抗体实现CD4或CD8 T细胞的耗竭。通过流式细胞术评估黏附分子水平。研究结果表明，在人类和小鼠的PD样本中均明显存在T细胞浸润。阻断CD4或CD8 T细胞可减轻小鼠PD的严重程度。与对照组相比，小鼠PD中细胞间黏附分子1（ICAM1或CD54）上调，其受体淋巴细胞功能相关抗原-1（LFA1）在PD小鼠脑内的T细胞中与对照组相比过表达。此外，抑制ICAM1或LFA1可减轻小鼠的PD相关特征。总之，ICAM1和LFA1之间的相互作用在将T细胞招募到中枢神经系统以介导实验性PD中起作用。
