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

Jonathan Chee, 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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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 isletspecific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific CD8 + T cells in NOD diabetes using MHCtetramer technology. IGRP 206-214-specific T cells in the peripheral lymphoid tissue increased with age, and their numbers correlated with insulitis progression. IGRP 206-214-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.

Original languageEnglish
Pages (from-to)572-580
Number of pages9
JournalJournal of Immunology
Volume192
Issue number2
DOIs
Publication statusPublished - 15 Jan 2014
Externally publishedYes

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Chee, J., Ko, H. J., Skowera, A., Jhala, G., Catterall, T., Graham, K. L., ... Krishnamurthy, B. (2014). Effector-memory T cells develop in islets and report islet pathology in type 1 diabetes. Journal of Immunology, 192(2), 572-580. https://doi.org/10.4049/jimmunol.1302100