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

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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
1939-327X
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
Subsets
Lymphocytes
Frequency
Tetramers
Susceptibility
Identification
Recognition
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 100326
100327
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
 
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