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

Cell Rep. 2020 Jun 30;31(13):107827. doi: 10.1016/j.celrep.2020.107827.


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.

Keywords: CD8(+) T cell; PD-1; PD-L1; PD-L2; acute infection; checkpoint blockade; effector; influenza; memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Death / immunology
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Immunologic Memory*
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Signal Transduction*
  • Species Specificity


  • Programmed Cell Death 1 Receptor