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

The Journal of Clinical Investigation
Lorraine YeoMark Peakman

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 insu...Continue Reading

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Citations

Aug 2, 2018·Nature Reviews. Endocrinology·Ivone Leong
Apr 2, 2020·Nature Immunology·Luca Petiti, Luigia Pace
Jul 4, 2020·Current Opinion in Endocrinology, Diabetes, and Obesity·Sefina ArifMartin Eichmann
Dec 10, 2019·The Journal of Clinical Investigation·Alice E WiedemanS Alice Long
May 15, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin EichmannCraig A Beam
Jul 4, 2020·Current Opinion in Endocrinology, Diabetes, and Obesity·Adeeb H Rahman, Dirk Homann
Jan 24, 2021·Immunology and Cell Biology·Alice E WiedemanSarah Alice Long
Feb 7, 2021·Immunology and Cell Biology·Chun-Ting J KwongBalasubramanian Krishnamurthy
Dec 29, 2020·Clinical and Experimental Immunology·M BattagliaT I Tree
Mar 21, 2021·Diabetes·Peter S LinsleyGerald T Nepom
Jun 12, 2021·The Journal of Experimental Medicine·Jeremy T WarshauerMark S Anderson
Aug 24, 2021·Frontiers in Immunology·Ranjeny ThomasSimi T Ahmed
Oct 7, 2021·Proceedings of the National Academy of Sciences of the United States of America·Amanda M AndersonMaki Nakayama

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Datasets Mentioned

BETA
E-MTAB-6727

Methods Mentioned

BETA
flow cytometry
FCS
FACS
RNA-Seq
PCA

Clinical Trials Mentioned

NCT00529399
NCT00505375
NCT00947427

Software Mentioned

SAS
Trimmomatic
HISAT2
FastQC
Picard Tools
GenePattern
R package clusterProfiler
CCA
tcR
DESeq2

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