Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30746
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dc.contributor.authorTsui, Carlson-
dc.contributor.authorKretschmer, Lorenz-
dc.contributor.authorRapelius, Svenja-
dc.contributor.authorGabriel, Sarah S-
dc.contributor.authorChisanga, David-
dc.contributor.authorKnöpper, Konrad-
dc.contributor.authorUtzschneider, Daniel T-
dc.contributor.authorNüssing, Simone-
dc.contributor.authorLiao, Yang-
dc.contributor.authorMason, Teisha-
dc.contributor.authorTorres, Santiago Valle-
dc.contributor.authorWilcox, Stephen A-
dc.contributor.authorKanev, Krystian-
dc.contributor.authorJarosch, Sebastian-
dc.contributor.authorLeube, Justin-
dc.contributor.authorNutt, Stephen L-
dc.contributor.authorZehn, Dietmar-
dc.contributor.authorParish, Ian A-
dc.contributor.authorKastenmüller, Wolfgang-
dc.contributor.authorShi, Wei-
dc.contributor.authorBuchholz, Veit R-
dc.contributor.authorKallies, Axel-
dc.date2022-
dc.date.accessioned2022-08-25T05:17:39Z-
dc.date.available2022-08-25T05:17:39Z-
dc.date.issued2022-08-17-
dc.identifier.citationNature 2022; 609(7926): 354-360en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/30746-
dc.description.abstractCD8+ T cells that respond to chronic viral infections or cancer are characterized by the expression of inhibitory receptors such as programmed cell death protein 1 (PD-1) and by the impaired production of cytokines. This state of restrained functionality-which is referred to as T cell exhaustion1,2-is maintained by precursors of exhausted T (TPEX) cells that express the transcription factor T cell factor 1 (TCF1), self-renew and give rise to TCF1- exhausted effector T cells3-6. Here we show that the long-term proliferative potential, multipotency and repopulation capacity of exhausted T cells during chronic infection are selectively preserved in a small population of transcriptionally distinct CD62L+ TPEX cells. The transcription factor MYB is not only essential for the development of CD62L+ TPEX cells and maintenance of the antiviral CD8+ T cell response, but also induces functional exhaustion and thereby prevents lethal immunopathology. Furthermore, the proliferative burst in response to PD-1 checkpoint inhibition originates exclusively from CD62L+ TPEX cells and depends on MYB. Our findings identify CD62L+ TPEX cells as a stem-like population that is central to the maintenance of long-term antiviral immunity and responsiveness to immunotherapy. Moreover, they show that MYB is a transcriptional orchestrator of two fundamental aspects of exhausted T cell responses: the downregulation of effector function and the long-term preservation of self-renewal capacity.en
dc.language.isoeng-
dc.titleMYB orchestrates T cell exhaustion and response to checkpoint inhibition.en
dc.typeJournal Articleen
dc.identifier.journaltitleNatureen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia..en
dc.identifier.affiliationDepartment of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia..en
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia..en
dc.identifier.affiliationDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia..en
dc.identifier.affiliationPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia..en
dc.identifier.affiliationSir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia..en
dc.identifier.affiliationSchool of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia..en
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationInstitute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany..en
dc.identifier.affiliationWürzburg Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-Universität Würzburg, Würzburg, Germany..en
dc.identifier.affiliationDivision of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany..en
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/35978192/en
dc.identifier.doi10.1038/s41586-022-05105-1en
dc.type.contentTexten
dc.identifier.orcidhttp://orcid.org/0000-0003-0642-814Xen
dc.identifier.orcidhttp://orcid.org/0000-0003-0987-8429en
dc.identifier.orcidhttp://orcid.org/0000-0002-0421-3957en
dc.identifier.orcidhttp://orcid.org/0000-0003-2076-2160en
dc.identifier.orcidhttp://orcid.org/0000-0003-2205-9057en
dc.identifier.orcidhttp://orcid.org/0000-0002-9746-2839en
dc.identifier.orcidhttp://orcid.org/0000-0002-2908-8590en
dc.identifier.orcidhttp://orcid.org/0000-0002-0020-6637en
dc.identifier.orcidhttp://orcid.org/0000-0003-1393-8527en
dc.identifier.orcidhttp://orcid.org/0000-0003-3528-478Xen
dc.identifier.orcidhttp://orcid.org/0000-0002-3835-1485en
dc.identifier.orcidhttp://orcid.org/0000-0003-0441-3913en
dc.identifier.orcidhttp://orcid.org/0000-0002-6312-6968en
dc.identifier.orcidhttp://orcid.org/0000-0003-1182-7735en
dc.identifier.pubmedid35978192-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
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