Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Ann Clin Transl Neurol. 2021 Jan;8(1):43-53. doi: 10.1002/acn3.51241. Epub 2020 Nov 24.
Our study aimed to investigate circulating CD8 T cell subpopulations and pro-inflammatory cytokines in the neuromyelitis optica spectrum disorder (NMOSD).
A total of 121 peripheral blood samples were obtained from 57 patients with NMOSD, 34 patients with multiple sclerosis (MS), and 30 sex- and age-matched healthy controls (HCs) for detection of CD8 T cell subpopulations, including phenotypes of naïve (T , CD62L CD45RO ), effector/memory (T , CD62L CD45RO ), memory precursor (T , CD127 KLRG1 ), and short lived effector (T , CD127 KLRG1 ). In addition, 36 samples from 18 NMOSD, 12 MS, and 6 sex- and age-matched HCs for detecting pro-inflammatory cytokines (IFNγ and TNFα) using flow cytometry.
Compared with HCs, we found significantly reduced CD8 T and increased CD8 T in both NMOSD and MS，while decreased CD8 T was only observed in NMOSD. Patients treated with immunotherapy were associated with increased CD8 T and decreased CD8 T in NMOSD. Moreover NMOSD cohort showed significant higher proportions of IFNγ CD8 T cells and proportions of TNFα CD8 T cells than HC and MS cohorts. On the contrary, obviously decreased IFNγ and TNFα were found in NMOSD patients treated with immunotherapy. Furthermore, Multivariate linear regression analyses revealed that age was negatively correlated with CD8 T and T , and positively associated with T ; however, sex, EDSS scores and disease phase were not significantly associated with CD8 T subpopulations.
This current study provides an evidence that circulating CD8 T cell with abnormal subpopulations and increased pro-inflammatory were associated with pathogenesis of autoimmune demyelinating disease of CNS, especially in NMOSD.
本研究旨在探讨视神经脊髓炎谱系疾病（NMOSD）患者外周血 CD8 T 细胞亚群和促炎细胞因子的变化。
共收集 57 例 NMOSD 患者、34 例多发性硬化（MS）患者和 30 名性别和年龄匹配的健康对照者（HC）外周血 121 份，检测 CD8 T 细胞亚群，包括幼稚（T ，CD62L CD45RO ）、效应/记忆（T ，CD62L CD45RO ）、记忆前体（T ，CD127 KLRG1 ）和短期存活效应（T ，CD127 KLRG1 ）亚群。另外，检测了 18 例 NMOSD、12 例 MS 和 6 名性别和年龄匹配的 HC 的 36 份样本，采用流式细胞术检测促炎细胞因子（IFNγ 和 TNFα）。
与 HC 相比，NMOSD 和 MS 患者外周血 CD8 T 细胞明显减少，CD8 T 细胞明显增多，而 NMOSD 患者仅表现为 CD8 T 细胞减少。NMOSD 患者经免疫治疗后，CD8 T 细胞增加，CD8 T 细胞减少。此外，NMOSD 组 IFNγ CD8 T 细胞比例和 TNFα CD8 T 细胞比例明显高于 HC 和 MS 组。相反，NMOSD 患者经免疫治疗后 IFNγ 和 TNFα 明显降低。进一步的多元线性回归分析显示，年龄与 CD8 T 细胞和 T 呈负相关，与 T 呈正相关；而性别、EDSS 评分和疾病阶段与 CD8 T 细胞亚群无显著相关性。
本研究表明，循环 CD8 T 细胞亚群异常和促炎细胞因子增加与中枢自身免疫脱髓鞘疾病的发病机制有关，特别是在 NMOSD 中。
