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Publication - Professor Colin Dayan

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

    Citation

    Skowera, A, Ladell, K, McLaren, JE, Dolton, G, Matthews, KK, Gostick, E, Kronenberg-Versteeg, D, Eichmann, M, Knight, RR, Heck, S, Powrie, J, Bingley, PJ, Dayan, CM, Miles, JJ, Sewell, AK, Price, DA & Peakman, M, 2015, ‘β-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure’. Diabetes, vol 64., pp. 916-25

    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.

    Full details in the University publications repository