title: Effector-memory T cells develop in islets and report islet pathology in type 1 diabetes.
abstract: CD8(+) T cells are critical in human type 1 diabetes and in the NOD mouse. In this study, we elucidated the natural history of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific CD8(+) T cells in NOD diabetes using MHC-tetramer technology. IGRP206-214-specific T cells in the peripheral lymphoid tissue increased with age, and their numbers correlated with insulitis progression. IGRP206-214-specific T cells in the peripheral lymphoid tissue expressed markers of chronic Ag stimulation, and their numbers were stable after diagnosis of diabetes, consistent with their memory phenotype. IGRP206-214-specific T cells in NOD mice expand, acquire the phenotype of effector-memory T cells in the islets, and emigrate to the peripheral lymphoid tissue. Our observations suggest that enumeration of effector-memory T cells of multiple autoantigen specificities in the periphery of type 1 diabetic subjects could be a reliable reporter for progression of islet pathology.
authors: St. Vincent's Institute, Fitzroy, Victoria 3065, Australia;
authors: Jonathan
authors: J
authors: Chee
authors: Hyun-Ja
authors: HJ
authors: Ko
authors: Ania
authors: A
authors: Skowera
authors: Gaurang
authors: G
authors: Jhala
authors: Tara
authors: T
authors: Catterall
authors: Kate L
authors: KL
authors: Graham
authors: Robyn M
authors: RM
authors: Sutherland
authors: Helen E
authors: HE
authors: Thomas
authors: Andrew M
authors: AM
authors: Lew
authors: Mark
authors: M
authors: Peakman
authors: Thomas W H
authors: TW
authors: Kay
authors: Balasubramanian
authors: B
authors: Krishnamurthy
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005952:Glucose-6-Phosphatase / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD
chemical_list: D001324:Autoantigens; D005952:Glucose-6-Phosphatase; C117983:G6pc2 protein, mouse