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PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity. | LitMetric

AI Article Synopsis

  • PD-1 is a protein found on exhausted T cells in cancer patients, and its role in these cells is not fully understood.
  • Research showed that PD-1 expression on CMV-specific CD4+ T cells varies between individuals and is stable over time, with higher levels correlating to viral load.
  • PD-1+ CD4+ T cells have high cytotoxic abilities but produce low levels of certain signaling molecules, potentially helping to control viral reactivation while reducing inflammation, highlighting the need for further study on PD-1's role in T cell exhaustion in cancer.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963093PMC
http://dx.doi.org/10.1371/journal.ppat.1009349DOI Listing

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