Journal article

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

J Chee, HJ Ko, A Skowera, G Jhala, T Catterall, KL Graham, RM Sutherland, HE Thomas, AM Lew, M Peakman, TWH Kay, B Krishnamurthy

Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 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 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 effec..

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Grants

Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia and the Juvenile Diabetes Research Foundation and was supported in part by the Victorian Government's Operational Infrastructure Support Program. M.P. and A.S. received funding from a United Kingdom National Institutes of Health Research Biomedical Research Centre award to Guy's and St Thomas' National Health Service Foundation Trust in partnership with King's College London.