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Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes.
- Source :
- Diabetes; Mar2017, Vol. 66 Issue 3, p722-734, 13p, 2 Diagrams, 2 Charts, 2 Graphs
- Publication Year :
- 2017
-
Abstract
- Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T cells from patients with type 1 diabetes. We identified hundreds of T cells from inflamed pancreatic islets of three young organ donors with type 1 diabetes with a short disease duration with high-risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture. Among 85 selected CD4 TCRs tested for reactivity to preproinsulin peptides presented by diabetes-susceptible HLA-DQ and HLA-DR molecules, one T cell recognized C-peptide amino acids 19-35, and two clones from separate donors responded to insulin B-chain amino acids 9-23 (B:9-23), which are known to be a critical self-antigen-driving disease progress in animal models of autoimmune diabetes. These B:9-23-specific T cells from islets responded to whole proinsulin and islets, whereas previously identified B:9-23 responsive clones from peripheral blood did not, highlighting the importance of proinsulin-specific T cells in the islet microenvironment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 66
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 121395446
- Full Text :
- https://doi.org/10.2337/db16-1025