Effector-memory T cells develop in islets and report islet pathology in type 1 diabetes - PubMed (original) (raw)

. 2014 Jan 15;192(2):572-80.

doi: 10.4049/jimmunol.1302100. Epub 2013 Dec 11.

Hyun-Ja Ko, Ania Skowera, Gaurang Jhala, Tara Catterall, Kate L Graham, Robyn M Sutherland, Helen E Thomas, Andrew M Lew, Mark Peakman, Thomas W H Kay, Balasubramanian Krishnamurthy

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

Jonathan Chee et al. J Immunol. 2014.

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.

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