Effector-memory T cells develop in islets and report islet pathology in type 1 diabetes

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 c...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2014-01, Vol.192 (2), p.572-580
Main Authors: Chee, Jonathan, Ko, Hyun-Ja, Skowera, Ania, Jhala, Gaurang, Catterall, Tara, Graham, Kate L, Sutherland, Robyn M, Thomas, Helen E, Lew, Andrew M, Peakman, Mark, Kay, Thomas W H, Krishnamurthy, Balasubramanian
Format: Article
Language:English
Subjects:
Animals
Autoantigens - immunology
CD8-Positive T-Lymphocytes - immunology
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 1 - pathology
Glucose-6-Phosphatase - immunology
Immunologic Memory - immunology
Islets of Langerhans - immunology
Islets of Langerhans - pathology
Lymphocytes - immunology
Mice
Mice, Inbred NOD
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1302100