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.
Competing Interests: Declaration of Interests A.H.S. and G.J.F. have patents/pending royalties on the PD-1 pathway from Roche, Merck, Bristol-Myers-Squibb, EMD-Serono, Boehringer-Ingelheim, AstraZeneca, Dako, and Novartis. G.J.F. has equity in Nextpoint, Triursus, and Xios. G.J.F. has served on advisory boards for Roche, Bristol-Myers-Squibb, Xios, and Origimed. A.H.S. is on advisory boards for Surface Oncology, Elstar, SQZ Biotechnologies, Selecta, Elpiscience, and Monopteros and has research funding from Novartis, Roche, Ipsen, Quark, and Merck. E.J.W. receives honoraria, consulting fees, and/or research support from BMS, Celgene, Dynavax, Eli Lilly, Elstar, Merck, MedImmune, Pieris, Roche, Surface Oncology, and KyMab. E.J.W. is a founder of Arsenal Biosciences. E.J.W. has a patent licensing agreement for the PD-1 pathway licensed by Genentech/Roche. W.N.H. is a founder of and equity holder at Arsenal Biosciences, equity holder at Tango therapeutics, and employee of Merck and Co.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)