PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity
Open Access
- 4 March 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 17 (3), e1009349
- https://doi.org/10.1371/journal.ppat.1009349
Abstract
PD-1 is expressed on exhausted T cells in cancer patients but its physiological role remains uncertain. We determined the phenotype, function and transcriptional correlates of PD-1 expression on cytomegalovirus-specific CD4+ T cells during latent infection. PD-1 expression ranged from 10–85% and remained stable over time within individual donors. This ‘setpoint’ was correlated with viral load at primary infection. PD-1+ CD4+ T cells display strong cytotoxic function but generate low levels of Th1 cytokines which is only partially reversed by PD-1 blockade. TCR clonotypes showed variable sharing between PD-1+ and PD-1- CMV-specific cells indicating that PD-1 status is defined either during T cell priming or subsequent clonal expansion. Physiological PD-1+ CD4+ T cells therefore display a unique ‘high cytotoxicity-low cytokine’ phenotype and may act to suppress viral reactivation whilst minimizing tissue inflammation. Improved understanding of the physiological role of PD-1 will help to delineate the mechanisms, and potential reversal, of PD-1+ CD4+ T cell exhaustion in patients with malignant disease.Keywords
Funding Information
- Medical Research Council (MR/R011230/1)
- Wellcome Trust (UNS29248)
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