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.
Preexisting Insulin Autoantibodies Predict Efficacy of Otelixizumab in Preserving Residual β-Cell Function in Recent-Onset Type 1 Diabetes
