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| Status |
Public on Nov 04, 2019 |
| Title |
Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TCR-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which neuroinflammation plays a critical function. Recurring viral infections and loss of immune competence increase risk for developing AD, yet the cellular and molecular mechanisms driving these immune changes are unknown. Here we performed mass cytometry of peripheral blood mononuclear cells and detected an immunologic signature of AD characterized by increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. CD8+ TEMRA cells were negatively associated with cognition and single cell RNA sequencing revealed their cytotoxic effector function. Strikingly, we discovered identical, shared T cell receptors (TCRs) of clonally expanded CD8+ TEMRA cells in cerebrospinal fluid (CSF) of three AD patients. Deep TCR sequencing, machine learning, and peptide screens identified the HLA-B*08:01-restricted Epstein-Barr virus trans-activator protein BZLF1 as the cognate antigen of a novel AD CSF TCR . These results provide the first evidence of clonal, antigen-specific T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration
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| |
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| Overall design |
Examination of transcriptional profile of cells from the cerbrospinal fluid of healthy and diseased patients.
AD = Alzheimer's disease
PD = Parkinson's disease
MCI = Mild cognitive impairment
HC = healthy control
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| |
|
| Contributor(s) |
Gate D, Leventhal O |
| Citation(s) |
31915375, 33482851 |
| Submission date |
Jul 29, 2019 |
| Last update date |
Feb 02, 2021 |
| Contact name |
Olivia Leventhal |
| E-mail(s) |
olevent1@stanford.edu, dgate@stanford.edu
|
| Organization name |
Stanford University
|
| Department |
Neurology
|
| Lab |
Wyss-Coray
|
| Street address |
1201 Welch Road, rm p220
|
| City |
Stanford |
| State/province |
California (CA) |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE134578 |
Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid |
|
| Relations |
| BioProject |
PRJNA557227 |
| SRA |
SRP216747 |
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