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. ORCID: https://orcid.org/0000-0003-3194-3135, 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

Preview

PDF - Published Version Download (6MB) | Preview

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:	06 May 2023 23:06
URI:	https://orca.cardiff.ac.uk/id/eprint/114342

Citation Data

Cited 31 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item