Title |
β-Cell–Specific CD8 T Cell Phenotype in Type 1 Diabetes Reflects Chronic Autoantigen Exposure
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Published in |
Diabetes, September 2014
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DOI | 10.2337/db14-0332 |
Pubmed ID | |
Authors |
Ania Skowera, Kristin Ladell, James E. McLaren, Garry Dolton, Katherine K. Matthews, Emma Gostick, Deborah Kronenberg-Versteeg, Martin Eichmann, Robin R. Knight, Susanne Heck, Jake Powrie, Polly J. Bingley, Colin M. Dayan, John J. Miles, Andrew K. Sewell, David A. Price, Mark Peakman |
Abstract |
Autoreactive CD8 T cells play a central role in the destruction of pancreatic islet β-cells that leads to type 1 diabetes, yet the key features of this immune-mediated process remain poorly defined. In this study, we combined high definition polychromatic flow cytometry with ultrasensitive peptide-human leukocyte antigen class I (pHLAI) tetramer staining to quantify and characterize β-cell-specific CD8 T cell populations in patients with recent onset type 1 diabetes and healthy controls. Remarkably, we found that β-cell-specific CD8 T cell frequencies in peripheral blood were similar between subject groups. In contrast to healthy controls, however, patients with newly diagnosed type 1 diabetes displayed hallmarks of antigen-driven expansion uniquely within the β-cell-specific CD8 T cell compartment. Molecular analysis of selected β-cell-specific CD8 T cell populations further revealed highly skewed oligoclonal T cell receptor (TCR) repertoires comprising exclusively private clonotypes. Collectively, these data identify novel and distinctive features of disease-relevant CD8 T cells that inform the immunopathogenesis of type 1 diabetes. |
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Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
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Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 15 | 15% |
Student > Master | 9 | 9% |
Student > Bachelor | 7 | 7% |
Professor | 5 | 5% |
Other | 18 | 17% |
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Agricultural and Biological Sciences | 15 | 15% |
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Unspecified | 2 | 2% |
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