Institute of Experimental Neurology and Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
Front Immunol. 2024 Jul 23;15:1436717. doi: 10.3389/fimmu.2024.1436717. eCollection 2024.
Neurological disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), may be associated with alterations in blood cell composition and phenotype. Here, we focused our attention on circulating mucosal-associated invariant T (MAIT) cells, a CD8 T cell memory population expressing the invariant Vα7.2 region in the T cell receptor and high surface levels of the CD161 marker. Transcriptomics data relative to peripheral blood mononuclear cells (PBMC) highlighted downregulation of CD161 and other MAIT-associated markers in progressive MS and not relapsing remitting (RR)-MS when gene expressions relative to each disease course were compared to those from healthy controls. Multiparametric flow cytometry of freshly isolated PBMC samples from untreated RR-MS, primary or secondary progressive MS (PP- or SP-MS), ALS and age- and sex-matched healthy controls revealed specific loss of circulating CD8 MAIT cells in PP-MS and no other MS courses or another neurological disorder such as ALS. Overall, these observations point to the existence of immunological changes in blood specific for the primary progressive course of MS that may support clinical definition of disease.
神经系统疾病,包括多发性硬化症(MS)和肌萎缩侧索硬化症(ALS),可能与血细胞组成和表型的改变有关。在这里,我们将注意力集中在循环粘膜相关不变 T(MAIT)细胞上,这是一种 CD8 T 细胞记忆群体,在 T 细胞受体中表达不变的 Vα7.2 区域和高水平的 CD161 标记物。与外周血单个核细胞(PBMC)相关的转录组学数据突出显示,与健康对照组相比,进展性 MS 而非复发性缓解型 MS(RR-MS)的 CD161 和其他 MAIT 相关标记物下调。对未经治疗的 RR-MS、原发性或继发性进行性 MS(PP-MS 或 SP-MS)、ALS 和年龄及性别匹配的健康对照组新鲜分离的 PBMC 样本进行多参数流式细胞术分析表明,PP-MS 中循环 CD8 MAIT 细胞特异性缺失,而其他 MS 病程或其他神经系统疾病(如 ALS)则没有。总的来说,这些观察结果表明,MS 原发性进行性病程存在针对血液的免疫变化,这可能支持疾病的临床定义。