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

摘要: 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 expression cytomegalovirus-specific CD4+ during latent infection. ranged from 10-85% remained stable over time within individual donors. This 'setpoint' was correlated with viral load at primary PD-1+ display strong cytotoxic generate low levels Th1 cytokines which only partially reversed by blockade. TCR clonotypes showed variable sharing between PD-1- CMV-specific indicating that status defined either cell priming or subsequent clonal expansion. Physiological therefore a unique 'high cytotoxicity-low cytokine' phenotype may act to suppress reactivation whilst minimizing tissue inflammation. Improved understanding will help delineate mechanisms, potential reversal, exhaustion malignant disease.