Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/24460
Title: Early precursor T cells establish and propagate T cell exhaustion in chronic infection.
Austin Authors: Utzschneider, Daniel T;Gabriel, Sarah S;Chisanga, David;Gloury, Renee;Gubser, Patrick M;Vasanthakumar, Ajithkumar;Shi, Wei;Kallies, Axel
Affiliation: Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Olivia Newton-John Cancer Research Institute
Department of Medical Biology, University of Melbourne, Melbourne, Australia
School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australia
School of Computing and Information Systems, University of Melbourne, Melbourne, Australia
Issue Date: 24-Aug-2020
Date: 2020-08-24
Publication information: Nature immunology 2020; 21(10): 1256-1266
Abstract: CD8+ T cells responding to chronic infections or tumors acquire an 'exhausted' state associated with elevated expression of inhibitory receptors, including PD-1, and impaired cytokine production. Exhausted T cells are continuously replenished by T cells with precursor characteristics that self-renew and depend on the transcription factor TCF1; however, their developmental requirements are poorly understood. In the present study, we demonstrate that high antigen load promoted the differentiation of precursor T cells, which acquired hallmarks of exhaustion within days of infection, whereas early effector cells retained polyfunctional features. Early precursor T cells showed epigenetic imprinting characteristic of T cell receptor-dependent transcription factor binding and were restricted to the generation of cells displaying exhaustion characteristics. Transcription factors BACH2 and BATF were key regulators with opposing functions in the generation of early precursor T cells. Overall, we demonstrate that exhaustion manifests first in TCF1+ precursor T cells and is propagated subsequently to the pool of antigen-specific T cells.
URI: https://ahro.austin.org.au/austinjspui/handle/1/24460
DOI: 10.1038/s41590-020-0760-z
ORCID: 0000-0003-2205-9057
0000-0002-0421-3957
0000-0002-1620-7781
0000-0002-6312-6968
Journal: Nature immunology
PubMed URL: 32839610
Type: Journal Article
Appears in Collections:Journal articles

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