β-Cell-specific CD8 T Cell phenotype in Type 1 diabetes reflects chronic autoantigen exposure

Skowera, Ania, Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, McLaren, James Edward ORCID: https://orcid.org/0000-0002-7021-5934, Dolton, Garry Michael, Matthews, Katherine K., Gostick, Emma, Kronenberg-Versteeg, Deborah, Eichmann, Martin, Knight, Robin R., Heck, Susanne, Powrie, Jake, Bingley, Polly J., Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462, Miles, John J., Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Price, David ORCID: https://orcid.org/0000-0001-9416-2737 and Peakman, Mark 2015. β-Cell-specific CD8 T Cell phenotype in Type 1 diabetes reflects chronic autoantigen exposure. Diabetes 64 (3) , pp. 916-925. 10.2337/db14-0332

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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 Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine
Publisher:	American Diabetes Association
ISSN:	0012-1797
Funders:	JDRF
Date of First Compliant Deposit:	22 July 2019
Date of Acceptance:	17 September 2014
Last Modified:	11 Nov 2024 19:15
URI:	https://orca.cardiff.ac.uk/id/eprint/79072

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