Table_1_Loss of Circulating CD8+ CD161high T Cells in Primary Progressive Multiple Sclerosis.pdf

Recent evidence suggests that the primary progressive form of multiple sclerosis (PP-MS) may present with specific immunological alterations. In this study we focused our attention on CD161, an NK and T cell marker upregulated in relapsing-remitting MS, and investigated its transcript and protein levels in blood cells from PP-MS and healthy individuals. We demonstrated transcriptional downregulation of CD161 in PP-MS and described concomitant mRNA reduction for RORgt, CCR6, CXCR6, KLRK1/NKG2D and many other markers typical of mucosa associated invariant T (MAIT) cells. Targeted multiparametric flow cytometry on fresh blood cells from an independent cohort of case-control subjects confirmed the selective loss of circulating CD8 CD161high T cells, which consist mainly of MAIT cells, and not of CD8 CD161int T cells in PP-MS. These data demonstrate alterations in a specific circulating immune cell subset in MS patients with progressive onset.

越来越多的研究证据表明，原发性进展型多发性硬化（primary progressive multiple sclerosis, PP-MS）可能存在特异性免疫学改变。本研究聚焦于CD161——一种在复发缓解型多发性硬化中表达上调的自然杀伤细胞（natural killer cell, NK）与T细胞标记物——并检测了原发性进展型多发性硬化患者与健康个体外周血细胞中CD161的转录本与蛋白水平。本研究证实原发性进展型多发性硬化患者体内CD161存在转录下调，并同步观测到视黄酸相关孤儿受体γt（RORgt）、CCR6、CXCR6、KLRK1/NKG2D以及诸多黏膜相关恒定T细胞（mucosa-associated invariant T, MAIT）标志性分子的mRNA水平降低。通过对独立病例-对照队列的新鲜血细胞开展靶向多参数流式细胞术（targeted multiparametric flow cytometry）分析，本研究进一步验证了原发性进展型多发性硬化患者体内循环CD8阳性CD161高表达T细胞（主要为黏膜相关恒定T细胞）的选择性丢失，而CD8阳性CD161中等表达T细胞并未出现此类异常。本研究数据证实，起病呈进展型的多发性硬化患者体内存在特定循环免疫细胞亚群的免疫学异常。