Beta-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 (2015) Beta-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure. Diabetes, 64 3: 916-925. doi:10.2337/db14-0332

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author 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.
Peakman, Mark
Title Beta-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure
Journal name Diabetes   Check publisher's open access policy
ISSN 0012-1797
Publication date 2015-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.2337/db14-0332
Open Access Status DOI
Volume 64
Issue 3
Start page 916
End page 925
Total pages 10
Place of publication Alexandria, VA, United States
Publisher American Diabetes Association
Language eng
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.
Keyword Recent onset
Double blind
Peptide Mhc
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 23 Sep 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 12 Apr 2015, 10:17:56 EST by System User on behalf of School of Medicine