%0 Journal Article %J Cell Reports %D 2020 %T The PD-1 Pathway Regulates Development and Function of Memory CD8+ T Cells following Respiratory Viral Infection %A Pauken, KE %A Godec, J %A Odorizzi, PM %A Brown, KE %A Yates, KB %A Ngiow, SF %A Burke, KP %A Freeman, G. J. %A Haining, WN %A Wherry, EJ %A Sharpe, A. H. %X

The PD-1 pathway regulates dysfunctional T cells in chronic infection and cancer, but the role of this pathway during acute infection remains less clear. Here, we demonstrate that PD-1 signals are needed for optimal memory. Mice deficient in the PD-1 pathway exhibit impaired CD8+ T cell memory following acute influenza infection, including reduced virus-specific CD8+ T cell numbers and compromised recall responses. PD-1 blockade during priming leads to similar differences early post-infection but without the defect in memory formation, suggesting that timing and/or duration of PD-1 blockade could be tailored to modulate host responses. Our studies reveal a role for PD-1 as an integrator of CD8+ T cell signals that promotes CD8+ T cell memory formation and suggest PD-1 continues to fine-tune CD8+ T cells after they migrate into nonlymphoid tissues. These findings have important implications for PD-1-based immunotherapy, in which PD-1 inhibition may influence memory responses in patients.

PubMed DOI

%B Cell Reports %V 31 %P 107827 %G eng %N 13