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Original Research
CD4 T Cells Reactive to Hybrid Insulin Peptides are Indicators of Disease Activity in the NOD Mouse
Rocky L. Baker, Braxton L. Jamison, Timothy A. Wiles, Robin S. Lindsay, Gene Barbour, Brenda Bradley, Thomas Delong, Rachel S. Friedman, Maki Nakayama and Kathryn Haskins
Diabetes 2018 Jun; db180200. https://doi.org/10.2337/db18-0200
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Abstract

We recently established that hybrid insulin peptides (HIPs), formed in islet beta-cells by fusion of insulin C-peptide fragments to peptides of Chromogranin A or Islet Amyloid Polypeptide, are ligands for diabetogenic CD4 T cell clones. The goal of this study was to investigate whether HIP-reactive T cells were indicative of ongoing autoimmunity. MHC class II tetramers were used to investigate the presence, phenotype and function of HIP-reactive and insulin-reactive T cells in non-obese diabetic (NOD) mice. Insulin-reactive T cells encounter their antigen early in disease, but they express FoxP3 and therefore may contribute to immune regulation. In contrast, HIP-reactive T cells are pro-inflammatory and highly diabetogenic in an adoptive transfer model. Because the frequency of antigen-experienced HIP-reactive T cells increases over progression of disease, they may serve as biomarkers of autoimmune diabetes.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-0200.

  • Received February 15, 2018.
  • Accepted June 20, 2018.
  • © 2018 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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March 2019
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CD4 T Cells Reactive to Hybrid Insulin Peptides are Indicators of Disease Activity in the NOD Mouse
Rocky L. Baker, Braxton L. Jamison, Timothy A. Wiles, Robin S. Lindsay, Gene Barbour, Brenda Bradley, Thomas Delong, Rachel S. Friedman, Maki Nakayama, Kathryn Haskins
Diabetes Jun 2018, db180200; DOI: 10.2337/db18-0200

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CD4 T Cells Reactive to Hybrid Insulin Peptides are Indicators of Disease Activity in the NOD Mouse
Rocky L. Baker, Braxton L. Jamison, Timothy A. Wiles, Robin S. Lindsay, Gene Barbour, Brenda Bradley, Thomas Delong, Rachel S. Friedman, Maki Nakayama, Kathryn Haskins
Diabetes Jun 2018, db180200; DOI: 10.2337/db18-0200
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© 2019 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.