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Cellular and molecular mechanisms of CD8+ T cell differentiation, dysfunction and exhaustion

journal contribution
posted on 17.11.2020, 00:53 by DJ Verdon, M Mulazzani, Misty Jenkins
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically “exhausted” in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

Funding

The authors would like to acknowledge the support of the Walter and Eliza Hall Institute of Medical Research. M.M. is funded by the German Cancer Aid (Mildred Scheel Postdoctoral Fellowship). M.R.J. is funded by NHMRC, The Walter and Eliza Hall Institute of Medical Research Suzanne Cory Fellowship, RCD Foundation and Cancer Australia

History

School

  • School of Molecular Sciences

Publication Date

05/10/2020

Journal

International Journal of Molecular Sciences

Volume

21

Issue

19

Article Number

7357

Pagination

28p. (p. 1-28)

Publisher

MDPI

ISSN

1422-0067

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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