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Diabetes. 2018 Sep;67(9):1836-1846. doi: 10.2337/db18-0200. Epub 2018 Jul 5.

CD4 T Cells Reactive to Hybrid Insulin Peptides Are Indicators of Disease Activity in the NOD Mouse.

Author information

1
Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO rocky.baker@ucdenver.edu katie.haskins@ucdenver.edu.
2
Department of Immunology and Microbiology, University of Colorado School of Medicine at Denver, Aurora, CO.
3
Department of Biomedical Research, National Jewish Health, Denver, CO.
4
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine at Denver, Aurora, CO.

Abstract

We recently established that hybrid insulin peptides (HIPs), formed in islet β-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 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 proinflammatory 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.

PMID:
29976617
PMCID:
PMC6110316
DOI:
10.2337/db18-0200
[Indexed for MEDLINE]
Free PMC Article

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