Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8 + T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8 + T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8 + T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8 + T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.

中文翻译：

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双胞胎研究确定了多发性硬化症中 CD8 + T 细胞的早期免疫和代谢失调


多发性硬化症 （MS） 是一种中枢神经系统的炎症性神经系统疾病，在明显的神经炎症之前有一个亚临床阶段。CD8 + T 细胞在 MS 病灶中丰富，但它们在疾病病理学中的潜在作用仍不清楚。使用高通量单细胞 RNA 测序和单细胞 T 细胞受体分析，我们比较了来自同卵双胞胎对血液和脑脊液 （CSF） 的 CD8 + T 细胞克隆，其中 cotwin 没有或亚临床神经炎症 （SCNI）。我们确定了外周 MS 相关的免疫和代谢改变，表明迁移、促炎和激活的 CD8 + T 细胞表型增强，这在患有 SCNI 的双胞胎和 MS 患者的独立验证队列中也很明显。总之，我们深入的单细胞分析表明浸润 CD8 + T 细胞的疾病驱动促炎作用，并在前驱和疾病的确定性阶段。