Loss of Circulating CD8+CD161high T Cells in Primary Progressive Multiple Sclerosis

Loss of Circulating CD8+CD161high T Cells in Primary Progressive Multiple Sclerosis
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DOI:
10.3389/fimmu.2019.01922
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发表时间:
2019-08-14
影响因子:
7.3
通讯作者:
Farina, Cinthia
Farina, Cinthia
中科院分区:
医学2区
文献类型:
--
作者:
Acquaviva, Massimo;Bassani, Claudia;Farina, Cinthia

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最近的证据表明,多发性硬化症(PP-MS)的原发进展型可能存在特定的免疫学改变。在这项研究中,我们将注意力集中在CD161,一种在复发-缓解期MS中上调的NK和T细胞标记物,并研究了它在PP-MS和健康人的血细胞中的转录和蛋白水平。我们证明了CD161在PP-MS中的转录下调,并描述了伴随的RORgt、CCR6、CXCR6、KLRK1/NKG2D和许多其他黏膜相关不变T(MAIT)细胞标志物的mRNA下调。靶向多参数流式细胞术对一组独立的病例对照受试者的新鲜血细胞进行检测,证实PP-MS中循环CD8 CD161(高)T细胞的选择性丢失,这些细胞主要由MAIT细胞组成,而不是CD8 CD161(Int)T细胞。这些数据表明,进行性起病的MS患者的特定循环免疫细胞亚群发生了变化。
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 CD161(high) T cells, which consist mainly of MAIT cells, and not of CD8 CD161(int) T cells in PP-MS. These data demonstrate alterations in a specific circulating immune cell subset in MS patients with progressive onset.