小柯机器人

美国斯坦福大学医学院Tony Wyss-Coray和David Gate研究团队合作发现，克隆性扩增的CD8 T细胞在阿尔茨海默病的脑脊液中“巡逻”。2020年1月8日，国际学术期刊《自然》在线发表了这一成果。

通过对多个数据集的综合分析，研究人员揭示了阿尔茨海默氏病外周和中枢适应性免疫的变化。首先，研究人员对外周血单个核细胞进行了大规模细胞计数，发现了阿尔茨海默氏病的免疫特征，其中包括CD8 ⁺ 效应T细胞记忆细胞CD45RA ⁺（TEMRA）数量增加。在第二个数据集中，研究人员发现CD8 ⁺ TEMRA细胞与认知呈负相关。

此外，单细胞RNA测序显示这些细胞中T细胞受体（TCR）信号增强。值得注意的是，通过对第三组数据进行几种单细胞TCR测序，研究人员发现阿尔茨海默氏病患者脑脊液中CD8 ⁺ TEMRA细胞克隆扩增。最后，利用机器学习、克隆和多肽筛选方法，研究人员证明阿尔茨海默氏病患者脑脊液中克隆扩增的TCR对两种单独爱泼斯坦-巴尔病毒抗原的特异性。这些结果揭示了阿尔茨海默氏病患者血液和脑脊液中的适应性免疫反应，并提供了克隆性、效应T细胞在与年龄相关的神经退行性疾病脑鞘内巡逻的证据。

据悉，阿尔茨海默氏病是一种不可治愈的神经退行性疾病，其中神经炎症对其发生起关键作用。然而，人们对适应性免疫反应在阿尔茨海默氏病中的作用知之甚少。

附：英文原文

Title: Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease

Author: David Gate, Naresha Saligrama, Olivia Leventhal, Andrew C. Yang, Michael S. Unger, Jinte Middeldorp, Kelly Chen, Benoit Lehallier, Divya Channappa, Mark B. De Los Santos, Alisha McBride, John Pluvinage, Fanny Elahi, Grace Kyin-Ye Tam, Yongha Kim, Michael Greicius, Anthony D. Wagner, Ludwig Aigner, Douglas R. Galasko, Mark M. Davis, Tony Wyss-Coray

Issue&Volume: 2020-01-08

Abstract: Alzheimer’s disease is an incurable neurodegenerative disorder in which neuroinflammation has a critical function1. However, little is known about the contribution of the adaptive immune response in Alzheimer’s disease2. Here, using integrated analyses of multiple cohorts, we identify peripheral and central adaptive immune changes in Alzheimer’s disease. First, we performed mass cytometry of peripheral blood mononuclear cells and discovered an immune signature of Alzheimer’s disease that consists of increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. In a second cohort, we found that CD8+ TEMRA cells were negatively associated with cognition. Furthermore, single-cell RNA sequencing revealed that T cell receptor (TCR) signalling was enhanced in these cells. Notably, by using several strategies of single-cell TCR sequencing in a third cohort, we discovered clonally expanded CD8+ TEMRA cells in the cerebrospinal fluid of patients with Alzheimer’s disease. Finally, we used machine learning, cloning and peptide screens to demonstrate the specificity of clonally expanded TCRs in the cerebrospinal fluid of patients with Alzheimer’s disease to two separate Epstein–Barr virus antigens. These results reveal an adaptive immune response in the blood and cerebrospinal fluid in Alzheimer’s disease and provide evidence of clonal, antigen-experienced T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration.

DOI: 10.1038/s41586-019-1895-7

Source: https://www.nature.com/articles/s41586-019-1895-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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