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dc.contributor.authorUtzschneider, Daniel T-
dc.contributor.authorGabriel, Sarah S-
dc.contributor.authorChisanga, David-
dc.contributor.authorGloury, Renee-
dc.contributor.authorGubser, Patrick M-
dc.contributor.authorVasanthakumar, Ajithkumar-
dc.contributor.authorShi, Wei-
dc.contributor.authorKallies, Axel-
dc.identifier.citationNature immunology 2020; 21(10): 1256-1266-
dc.description.abstractCD8+ 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.-
dc.titleEarly precursor T cells establish and propagate T cell exhaustion in chronic infection.-
dc.typeJournal Articleen
dc.identifier.journaltitleNature immunology-
dc.identifier.affiliationDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australiaen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationDepartment of Medical Biology, University of Melbourne, Melbourne, Australiaen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationSchool of Computing and Information Systems, University of Melbourne, Melbourne, Australiaen
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item.openairetypeJournal Article-
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