biostudies-literatureSkowera ANational Institute for Health Research (NIHR)Juvenile Diabetes Research FoundationWellcome TrustJuvenile Diabetes Research Foundation (JDRF) Autoimmunity Centers Consortium916-925https://www.ebi.ac.uk/biostudies/studies/S-EPMC4557541biostudies-literatureUnknown64(3)Autoreactive CD8 T cells play a central role in the destruction of pancreatic islet β-cells that leads to type 1 diabetes, yet the key features of this immune-mediated process remain poorly defined. In this study, we combined high-definition polychromatic flow cytometry with ultrasensitive peptide-human leukocyte antigen class I tetramer staining to quantify and characterize β-cell-specific CD8 T cell populations in patients with recent-onset type 1 diabetes and healthy control subjects. Remarkably, we found that β-cell-specific CD8 T cell frequencies in peripheral blood were similar between subject groups. In contrast to healthy control subjects, however, patients with newly diagnosed type 1 diabetes displayed hallmarks of antigen-driven expansion uniquely within the β-cell-specific CD8 TDiabetesβ-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure.PMC4557541100326/Z/12/Ztype 1 diabetes 21719417-2012-3521-2007-1803100326100327Heck SSkowera ASewell AKMcLaren JEPrice DAEichmann MBingley PJDayan CMPeakman MMatthews KKKronenberg-Versteeg DPowrie JMiles JJDolton GLadell KKnight RRGostick Efalseβ-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure.Autoreactive CD8 T cells play a central role in the destruction of pancreatic islet β-cells that leads to type 1 diabetes, yet the key features of this immune-mediated process remain poorly defined. In this study, we combined high-definition polychromatic flow cytometry with ultrasensitive peptide-human leukocyte antigen class I tetramer staining to quantify and characterize β-cell-specific CD8 T cell populations in patients with recent-onset type 1 diabetes and healthy control subjects. Remarkably, we found that β-cell-specific CD8 T cell frequencies in peripheral blood were similar between subject groups. In contrast to healthy control subjects, however, patients with newly diagnosed type 1 diabetes displayed hallmarks of antigen-driven expansion uniquely within the β-cell-specific CD8 T2015-01-01T00:00:00Z2015 Mar2025-04-26T04:04:54.63Z2019-03-27T01:57:42ZS-EPMC45575412524957910.2337/db14-0332