The PD-1 Pathway Regulates Development and Function of Memory CD8+ T Cells following Respiratory Viral Infection

Abstract

The PD-1 pathway regulates dysfunctional Tcells 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+ Tcell memory following acute influenza infection, including reduced virus-specific CD8+ Tcell 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+ Tcell signals that promotes CD8+ Tcell memory formation and suggest PD-1 continues to fine-tune CD8+ Tcells after they migrate into non-lymphoid tissues. These findings have important implications for PD-1-based immunotherapy, in which PD-1 inhibition may influence memory responses in patients.