...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease
【24h】

Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease

机译：克隆扩增的CD8 T细胞在阿尔茨海默氏病中巡查脑脊液

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Alzheimer's disease is an incurable neurodegenerative disorder in which neuroinflammation has a critical function(1). However, little is known about the contribution of the adaptive immune response in Alzheimer's disease(2). 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(+) (T-EMRA) cells. In a second cohort, we found that CD8(+) T-EMRA 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(+) T-EMRA 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.
机译：阿尔茨海默氏病是一种不可治愈的神经退行性疾病，其中神经炎症具有关键功能（1）。但是，关于适应性免疫反应在阿尔茨海默氏病中的作用了解甚少（2）。在这里，通过对多个队列的综合分析，我们确定了阿尔茨海默氏病的外周和中枢适应性免疫变化。首先，我们进行了外周血单个核细胞的大规模细胞计数，发现了阿尔茨海默氏病的免疫特征，其中包括数量增加的CD8（+）T效应记忆CD45RA（+）（T-EMRA）细胞。在第二个队列中，我们发现CD8（+）T-EMRA细胞与认知呈负相关。此外，单细胞RNA测序显示这些细胞中的T细胞受体（TCR）信号增强。值得注意的是，在第三组研究中，通过使用单细胞TCR测序的几种策略，我们在阿尔茨海默氏病患者的脑脊液中发现了克隆扩增的CD8（+）T-EMRA细胞。最后，我们使用机器学习，克隆和多肽筛选来证明阿尔茨海默氏病患者脑脊液中克隆扩增的TCR对两种单独的爱泼斯坦-巴尔病毒抗原的特异性。这些结果揭示了阿尔茨海默氏病在血液和脑脊液中的适应性免疫反应，并提供了克隆的，抗原经历的T细胞在年龄相关的神经变性影响的大脑鞘内空间巡逻的证据。

著录项

  • 来源
    《Nature》 |2020年第7790期|399-404|共6页
  • 作者

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

  • 作者单位

    Stanford Univ Sch Med Dept Neurol & Neurol Sci Stanford CA 94305 USA|Vet Adm Palo Alto Healthcare Syst Palo Alto CA 94304 USA;

    Stanford Univ Dept Microbiol & Immunol Sch Med Stanford CA 94305 USA;

    Stanford Univ Sch Med Dept Neurol & Neurol Sci Stanford CA 94305 USA;

    Stanford Univ Dept Bioengn Stanford CA 94305 USA|Stanford Univ Chem Engn & Med Human Hlth Stanford CA 94305 USA;

    Paracelsus Med Univ Inst Mol Regenerat Med Salzburg Austria|Paracelsus Med Univ Spinal Cord Injury & Tissue Regenerat Ctr Salzbur Salzburg Austria;

    Stanford Univ Sch Med Dept Neurol & Neurol Sci Stanford CA 94305 USA|Vet Adm Palo Alto Healthcare Syst Palo Alto CA 94304 USA|Univ Utrecht Univ Med Ctr Utrecht Dept Translat Neurosci Brain Ctr Utrecht Netherlands;

    Stanford Univ Sch Med Dept Neurol & Neurol Sci Stanford CA 94305 USA|Stanford Univ Sch Med Med Scientist Training Program Stanford CA 94305 USA|Stanford Univ Sch Med Stem Cell Biol & Regenerat Med Grad Program Stanford CA 94305 USA;

    Univ Calif San Francisco Dept Neurol Memory & Aging Ctr San Francisco CA USA;

    Stanford Univ Sch Med Dept Neurol & Neurol Sci Stanford CA 94305 USA|Stanford Univ Dept Neurol & Neurol Sci Sch Med Funct Imaging Neuropsychiat Disorders Lab Stanford CA 94305 USA;

    Stanford Univ Dept Psychol Stanford CA USA|Stanford Univ Wu Tsai Neurosci Inst Stanford CA 94305 USA;

    Univ Calif San Diego Dept Neurosci La Jolla CA 92093 USA;

    Stanford Univ Dept Microbiol & Immunol Sch Med Stanford CA 94305 USA|Stanford Univ Sch Med Inst Immun Transplantat & Infect Stanford CA 94305 USA|Stanford Univ Howard Hughes Med Inst Sch Med Stanford CA 94305 USA;

    Stanford Univ Sch Med Dept Neurol & Neurol Sci Stanford CA 94305 USA|Vet Adm Palo Alto Healthcare Syst Palo Alto CA 94304 USA|Stanford Univ Chem Engn & Med Human Hlth Stanford CA 94305 USA|Stanford Univ Wu Tsai Neurosci Inst Stanford CA 94305 USA|Stanford Univ Sch Med Paul F Glenn Ctr Biol Aging Stanford CA 94305 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号