Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion

Version 1 : Received: 31 August 2020 / Approved: 31 August 2020 / Online: 31 August 2020 (17:49:37 CEST)

How to cite: Verdon, D.J.; Mulazzani, M.; Jenkins, M.R. Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion. Preprints 2020, 2020080728 (doi: 10.20944/preprints202008.0728.v1). Verdon, D.J.; Mulazzani, M.; Jenkins, M.R. Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion. Preprints 2020, 2020080728 (doi: 10.20944/preprints202008.0728.v1).

Abstract

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.

Subject Areas

T cell exhaustion; chronic viral infections; cancer; immunotherapy; epigenetics; PD-1; inhibitory receptors

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