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One in Ten CD8+ Cells in the Pancreas of Living Individuals With Recent Onset Type 1 Diabetes Recognizes the Preproinsulin Epitope PPI15-24

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posted on 07.01.2021, 19:40 by Ada AdminAda Admin, Teresa Rodriguez-Calvo, Lars Krogvold, Natalie Amirian, Knut Dahl-Jørgensen, Matthias von Herrath
In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with short and long disease duration. The Diabetes Virus Detection (DiViD) study collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset type 1 diabetes. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8+ T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We additionally show the heterogeneity of islet distribution and CD8+ T cell infiltration. Our findings contribute to the current limited existing knowledge on T cell reactivity in the pancreas of recent onset type 1 diabetic donors, and indicate that antigen-specific therapies directed towards preproinsulin could have high clinical impact.

Funding

This work was supported by the National Institutes of Health (NIH), grant # R01 AI092453 to M.v.H. K.D-J is the Principal Investigator of the DiViD study and is funded by the South-Eastern Norway Regional Health Authority, the Novo Nordisk Foundation, and through the PEVNET (Persistent Virus Infection in Diabetes Network) Study Group funded by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 261441 PEVNET.

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