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

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)916-25
Number of pages10
JournalDiabetes
Volume64
Issue number3
Early online date23 Sep 2014
DOIs
E-pub ahead of print23 Sep 2014
PublishedMar 2015

King's Authors

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.

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