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

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

Research output: Contribution to journalArticle (Academic Journal)peer-review

56 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)916-25
Number of pages10
JournalDiabetes
Volume64
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • Adult
  • Autoantigens
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Diabetes Mellitus, Type 1
  • Female
  • Flow Cytometry
  • Glutamate Decarboxylase
  • Humans
  • Insulin-Secreting Cells
  • Male
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8

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