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Autoreactive T effector memory differentiation mirrors b cell function in type 1 diabetes

Yeo, Lorraine, Woodwyk, Alyssa, Sood, Sanjana, Lorenc, Anna, Eichmann, Martin, Pujol-Autonell, Irma, Melchiotti, Rosella, Skowera, Ania, Fidanis, Efthymios, Dolton, Garry M., Tungatt, Katie, Sewell, Andrew K., Heck, Susanne, Saxena, Alka, Beam, Craig A. and Peakman, Mark 2018. Autoreactive T effector memory differentiation mirrors b cell function in type 1 diabetes. Journal of Clinical Investigation 128 (8) , pp. 3460-3474. 10.1172/JCI120555

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Abstract

In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell–reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell–reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell–specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57– counterparts, and network association modeling indicated that the dynamics of β cell–reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating β cell–specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Date of First Compliant Deposit: 23 August 2018
Date of Acceptance: 23 May 2018
Last Modified: 11 Jun 2020 16:30
URI: http://orca.cf.ac.uk/id/eprint/114342

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