Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion
1
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
2
Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
3
Institute of Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7357; https://doi.org/10.3390/ijms21197357
Received: 31 August 2020 / Revised: 1 October 2020 / Accepted: 2 October 2020 / Published: 5 October 2020
(This article belongs to the Special Issue Recent Advances in T Cell Immunity)
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.
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Keywords:
T cell exhaustion; chronic viral infections; cancer; immunotherapy; epigenetics; PD-1; inhibitory receptors
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MDPI and ACS Style
Verdon, D.J.; Mulazzani, M.; Jenkins, M.R. Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion. Int. J. Mol. Sci. 2020, 21, 7357. https://doi.org/10.3390/ijms21197357
AMA Style
Verdon DJ, Mulazzani M, Jenkins MR. Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion. International Journal of Molecular Sciences. 2020; 21(19):7357. https://doi.org/10.3390/ijms21197357
Chicago/Turabian StyleVerdon, Daniel J., Matthias Mulazzani, and Misty R. Jenkins 2020. "Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion" International Journal of Molecular Sciences 21, no. 19: 7357. https://doi.org/10.3390/ijms21197357
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