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Resident Memory-like CD8+ T Cells Are Involved in Chronic Inflammatory and Neurodegenerative Diseases in the CNS
Neurology Neuroimmunology & Neuroinflammation ( IF 8.8 ) Pub Date : 2024-01-01 , DOI: 10.1212/nxi.0000000000200172
Kimitoshi Kimura 1 , Ryusei Nishigori 1 , Mio Hamatani 1 , Masanori Sawamura 1 , Shinji Ashida 1 , Chihiro Fujii 1 , Masaki Takata 1 , Youwei Lin 1 , Wakiro Sato 1 , Tomoko Okamoto 1 , Akira Kuzuya 1 , Ryosuke Takahashi 1 , Takashi Yamamura 1 , Takayuki Kondo 1
Affiliation  

Background and Objectives

Resident memory T (Trm) cells are a unique population that can survive and function in a compartmentalized tissue with inflammatory potential. We aim to investigate the alteration of Trm population in acute/chronic inflammatory and neurodegenerative diseases in the CNS.

Methods

The frequencies of CD4+ and CD8+ T cells expressing both CD69 and CD103, the markers for Trm cells, were quantified in the peripheral blood and CSF (n = 80 and 44, respectively) in a cross-sectional manner. The transcriptional profile of Trm-like population in the CSF was further analyzed using a public single-cell dataset.

Results

The frequency of CD69+CD103+CD8+ T cells was strikingly higher in the CSF than in the peripheral blood (among memory fraction, 13.5% vs 0.11%, difference (mean [SE]): 13.4% [2.9]). This CD69+CD103+CD8+ T-cell population was increased in the CSF from patients with chronic inflammatory diseases including multiple sclerosis and with neurodegenerative diseases such as Parkinson disease and Alzheimer disease compared with controls (11.5%, 13.0%, 8.1% vs 2.9%, respectively). By contrast, the frequency was not altered in acute inflammatory conditions in the CNS (4.0%). Single-cell RNAseq analysis confirmed Trm signature in CD69+CD103+CD8+ T cells in the CSF, supporting their Trm-like phenotype, which was not clear in controls.

Discussion

Collectively, an increase in CD69+CD103+CD8+ Trm-like population in the CSF is related with both chronic neuroinflammatory and some neurodegenerative diseases in the CNS, suggesting a partially shared pathology in these diseases.



中文翻译:

常驻记忆样 CD8+ T 细胞参与中枢神经系统慢性炎症和神经退行性疾病

背景和目标

常驻记忆 T (Trm) 细胞是一种独特的细胞群,可以在具有炎症潜力的分隔组织中存活并发挥作用。我们的目的是研究中枢神经系统急性/慢性炎症和神经退行性疾病中 Trm 群体的变化。

方法

以横断面方式对外周血和脑脊液中表达 CD69 和 CD103(Trm 细胞标记物)的 CD4 + 和 CD8 + T细胞的频率进行定量(分别为 n = 80 和 44)。使用公共单细胞数据集进一步分析了 CSF 中 Trm 样群体的转录谱。

结果

脑脊液中 CD69 + CD103 + CD8 + T 细胞的频率明显高于外周血(记忆分数中,13.5% vs 0.11%,差异(平均值 [SE]):13.4% [2.9])。与对照组相比,患有包括多发性硬化症在内的慢性炎症性疾病以及帕金森病和阿尔茨海默病等神经退行性疾病的患者脑脊液中的CD69 + CD103 + CD8 + T 细胞群有所增加(11.5%、13.0%、8.1% vs 2.9%) %, 分别)。相比之下,中枢神经系统急性炎症情况下的频率没有改变(4.0%)。单细胞 RNAseq 分析证实了脑脊液中 CD69 + CD103 + CD8 + T 细胞中的 Trm 特征,支持它们的 Trm 样表型,这在对照中尚不清楚。

讨论

总的来说,CSF 中 CD69 + CD103 + CD8 + Trm 样群体的增加与 CNS 中的慢性神经炎症和一些神经退行性疾病有关,表明这些疾病具有部分共同的病理学。

更新日期:2023-11-11
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