Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, 200065, Shanghai, People's Republic of China.
Department of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China.
J Neurol. 2022 Oct;269(10):5368-5381. doi: 10.1007/s00415-022-11190-z. Epub 2022 May 24.
T lymphocytes are involved in the pathogenesis of Parkinson's disease (PD), while the heterogeneity of T-cell subpopulations remains elusive. In this study, we analyzed up to 22 subpopulations of T lymphocytes in 115 PD patients and 60 matched healthy controls (HC) using flow cytometry. We found that PD patients exhibited decreased naïve CD8 T cells (CD3 CD8 CD45RA CD45RO) and increased late-differentiated CD4 T cells (CD3 CD4 CD28 CD27), compared to HC, which were not affected by anti-parkinsonism medication administration. The proportion of naïve CD8 T cells in PD patients was positively correlated with their severity of autonomic dysfunction and psychiatric complications, but negatively associated with the severity of rapid eye movement and sleep behavior disorder. The proportion of late-differentiated CD4 T cells was negatively correlated with the onset age of the disease. We further developed individualized PD risk prediction models with high reliability and accuracy on the base of the T lymphocyte subpopulations. These data suggest that peripheral cellular immunity is disturbed in PD patients, and changes in CD8 T cells and late-differentiated CD4 T cells are representative and significant. Therefore, we recommend naïve CD8 + and late-differentiated CD4 T cells as candidates for multicentric clinical study and pathomechanism study of PD.
T 淋巴细胞参与帕金森病(PD)的发病机制,而 T 细胞亚群的异质性仍不清楚。在这项研究中,我们使用流式细胞术分析了 115 名 PD 患者和 60 名匹配的健康对照者(HC)多达 22 种 T 淋巴细胞亚群。与 HC 相比,PD 患者表现出幼稚 CD8+T 细胞(CD3+CD8+CD45RA+CD45RO)减少和晚期分化的 CD4+T 细胞(CD3+CD4+CD28+CD27)增加,而抗帕金森病药物治疗并不影响这些变化。PD 患者幼稚 CD8+T 细胞的比例与自主神经功能障碍和精神并发症的严重程度呈正相关,与快速眼动和睡眠行为障碍的严重程度呈负相关。晚期分化的 CD4+T 细胞的比例与疾病的发病年龄呈负相关。在此基础上,我们进一步建立了基于 T 淋巴细胞亚群的具有高可靠性和准确性的个体化 PD 风险预测模型。这些数据表明,PD 患者外周细胞免疫受到干扰,CD8+T 细胞和晚期分化的 CD4+T 细胞的变化具有代表性和显著性。因此,我们建议将幼稚 CD8+和晚期分化的 CD4+T 细胞作为 PD 多中心临床研究和发病机制研究的候选者。