β-cell–specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure

Skowera, Ania, Ladell, Kristin, McLaren, James E., Dolton, Garry, Matthews, Katherine K., Gostick, Emma, Kronenberg-Versteeg, Deborah, Eichmann, Martin, Knight, Robin R., Heck, Susanne, Powrie, Jake, Bingley, Polly J., Dayan, Colin M., Miles, John J., Sewell, Andrew K., Price, David A., and Peakman, Mark (2014) β-cell–specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure. Diabetes, 64 (3). pp. 916-925.

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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 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.

Item ID: 45055
Item Type: Article (Research - C1)
ISSN: 1939-327X
Funders: National Institute for Health Research (NIHR), JDRF Autoimmunity Centers Consortium (ACC), JDRF, National Health and Medical Research Council of Australia (NHMRC), Wellcome Trust, European Commission (EC)
Projects and Grants: ACC 1-2007-1803 , JDRF award 217194 17-2012-35, EC Seventh Framework Programm
Date Deposited: 11 Aug 2016 02:41
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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