Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer&#39;s disease

doi:10.1038/s41586-019-1895-7

GSTDTAP > 地球科学

DOI	10.1038/s41586-019-1895-7
	Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease
	Gate, David 1,2; Saligrama, Naresha 3; Leventhal, Olivia 1; Yang, Andrew C.4,5; Unger, Michael S.6,7; Middeldorp, Jinte 1,2,8; Chen, Kelly 1; Lehallier, Benoit 1,2; Channappa, Divya 1; De Los Santos, Mark B.1; McBride, Alisha 1,2; Pluvinage, John 1,9,10; Elahi, Fanny 11; Tam, Grace Kyin-Ye 1,12; Kim, Yongha 1,12; Greicius, Michael 1,12; Wagner, Anthony D.13,14; Aigner, Ludwig 6,7; Galasko, Douglas R.15; Davis, Mark M.3,16,17; Wyss-Coray, Tony 1,2,5,14,18
	2020-06-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	577 期号:7790 页码:399-+
文章类型	Article
语种	英语
国家	USA; Austria; Netherlands
英文关键词	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.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000509570100038
WOS关键词	CENTRAL MEMORY ; RECEPTOR ; REACTIVITY ; SUBSETS ; CD4(+)
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281021
专题	地球科学资源环境科学气候变化
作者单位	1.Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA; 2.Vet Adm Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA; 3.Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA; 4.Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA; 5.Stanford Univ, Chem Engn & Med Human Hlth, Stanford, CA 94305 USA; 6.Paracelsus Med Univ, Inst Mol Regenerat Med, Salzburg, Austria; 7.Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Salzburg, Austria; 8.Univ Utrecht, Univ Med Ctr Utrecht Brain Ctr, Dept Translat Neurosci, Utrecht, Netherlands; 9.Stanford Univ, Med Scientist Training Program, Sch Med, Stanford, CA 94305 USA; 10.Stanford Univ, Stem Cell Biol & Regenerat Med Grad Program, Sch Med, Stanford, CA 94305 USA; 11.Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA; 12.Stanford Univ, Funct Imaging Neuropsychiat Disorders Lab, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA; 13.Stanford Univ, Dept Psychol, Stanford, CA USA; 14.Stanford Univ, Wu Tsai Neurosci Inst, Stanford, CA 94305 USA; 15.Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA; 16.Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA; 17.Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA; 18.Stanford Univ, Paul Glenn Ctr Biol Aging, Sch Med, Stanford, CA 94305 USA
推荐引用方式 GB/T 7714	Gate, David,Saligrama, Naresha,Leventhal, Olivia,et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease[J]. NATURE,2020,577(7790):399-+.
APA	Gate, David.,Saligrama, Naresha.,Leventhal, Olivia.,Yang, Andrew C..,Unger, Michael S..,...&Wyss-Coray, Tony.(2020).Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease.NATURE,577(7790),399-+.
MLA	Gate, David,et al."Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease".NATURE 577.7790(2020):399-+.