β-Cell–Specific CD8 T Cell Phenotype in Type 1 Diabetes Reflects Chronic Autoantigen Exposure
| العنوان: | β-Cell–Specific CD8 T Cell Phenotype in Type 1 Diabetes Reflects Chronic Autoantigen Exposure |
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| المؤلفون: | James E. McLaren, Kristin Ladell, Emma Gostick, Robin R. Knight, Ania Skowera, David Price, Katherine K. Matthews, Martin Eichmann, Andrew K. Sewell, Deborah Kronenberg-Versteeg, Garry Dolton, Colin M. Dayan, Polly J. Bingley, Mark Peakman, Susanne Heck, Jake Powrie, John J. Miles |
| المصدر: | Diabetes. 64:916-925 |
| بيانات النشر: | American Diabetes Association, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, Endocrinology, Diabetes and Metabolism, Cellular differentiation, Human leukocyte antigen, CD8-Positive T-Lymphocytes, Biology, Autoantigens, Article, Flow cytometry, Insulin-Secreting Cells, Diabetes mellitus, Internal Medicine, medicine, Humans, Cytotoxic T cell, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Type 1 diabetes, medicine.diagnostic_test, Glutamate Decarboxylase, T-cell receptor, Cell Differentiation, Flow Cytometry, medicine.disease, Phenotype, Diabetes Mellitus, Type 1, QR180, Immunology, Female, RC |
| الوصف: | 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 tetramer staining to quantify and characterize β-cell–specific CD8 T cell populations in patients with recent-onset type 1 diabetes and healthy control subjects. Remarkably, we found that β-cell–specific CD8 T cell frequencies in peripheral blood were similar between subject groups. In contrast to healthy control subjects, 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 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1939-327X 0012-1797 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36dea629812a2376ea48ed423fab9e41 https://doi.org/10.2337/db14-0332 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....36dea629812a2376ea48ed423fab9e41 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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