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

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 non-lymphoid tissues. These findings have important implications for PD-1-based immunotherapy, in which PD-1 inhibition may influence memory responses in patients.