The Transcription Factor TCF1 Preserves the Effector Function of Exhausted CD8 T Cells During Chronic Viral Infection

Frontiers in Immunology
Yifei WangLifan Xu

Abstract

The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells.

References

Dec 22, 1998·The Journal of Experimental Medicine·A J ZajacR Ahmed
Feb 4, 2003·Nature Immunology·E John WherryRafi Ahmed
Jul 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hirohito IchiiTakeshi Tokuhisa
Nov 24, 2004·Trends in Pharmacological Sciences·Laurent MeijerPaul Greengard
Nov 28, 2006·European Journal of Immunology·Kazuki YoshidaTakeshi Tokuhisa
Oct 9, 2007·Journal of Virological Methods·Megan M McCausland, Shane Crotty
Jul 15, 2009·Cell·Herbert W VirginRafi Ahmed
Dec 23, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dong-Mei ZhaoHai-Hui Xue
Jan 19, 2010·Immunologic Research·Qing YuJyoti Misra Sen
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Grégoire JeannetWerner Held
Jul 20, 2010·Immunological Reviews·Jill M Angelosanto, E John Wherry
Oct 29, 2010·The Journal of Biological Chemistry·Elisabeth MaierJutta Horejs-Hoeck
Jul 9, 2011·Nature Immunology·E John Wherry
Aug 10, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xinyuan Zhou, Hai-Hui Xue
Mar 29, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Frederick MassonGabrielle T Belz
Apr 20, 2013·Nature Reviews. Immunology·David Masopust, Jason M Schenkel
Feb 11, 2015·Annual Review of Immunology·Maria Elena De Obaldia, Avinash Bhandoola
Feb 15, 2015·Immunity·Gustavo J MartinezAnjana Rao
Jan 6, 2016·The Journal of Clinical Investigation·R Brad Jones, Bruce D Walker
Feb 2, 2016·Current Opinion in Virology·Dietmar ZehnRobert Thimme
Mar 24, 2016·Nature Immunology·Chih-Hao Chang, Erika L Pearce
Aug 17, 2016·Nature Reviews. Immunology·Daniel E SpeiserGrégory Verdeil
Oct 30, 2016·Science·Debattama R SenW Nicholas Haining

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Citations

Feb 19, 2020·Nature Immunology·Joanna MikulakDomenico Mavilio
Sep 26, 2020·International Journal of Molecular Sciences·Heather M Ren, Aron E Lukacher
Jul 15, 2020·Nature Immunology·Chang LiuDario A A Vignali
Jun 18, 2020·Frontiers in Immunology·Alexander YermanosAnnette Oxenius
Nov 8, 2020·Science Immunology·Giulia EscobarAna C Anderson
Feb 28, 2021·Science Immunology·Elyse A WatkinsJeffrey A Hubbell
Apr 30, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiaxue ZhangHui Feng
Jun 16, 2021·Nature Reviews. Immunology·Xudong ZhaoHai-Hui Xue
Oct 30, 2021·Cancer Cell·Lewis AuUNKNOWN TRACERx Renal Consortium
Jun 16, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexandra M MiggelbrinkPeter E Fecci

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Methods Mentioned

BETA
Knockout
transgenic
flow cytometry
FACS
transfection
PCR

Software Mentioned

GraphPad
FlowJo
Prism
Morpheus

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