Regulation of human and mouse bystander T cell activation responses by PD-1

Catherine T. Le, Logan V. Vick, Craig Collins, Cordelia Dunai, Michael K. Sheng, Lam T. Khuat, Isabel Barao, Sean J. Judge, Ethan G. Aguilar, Brendan Curti, Maneesh Dave, Dan L. Longo, Bruce R. Blazar, Robert J. Canter, Arta M. Monjazeb, William J. Murphy

Research output: Contribution to journalArticlepeer-review


Bystander activation of memory T cells occurs via cytokine signaling alone in the absence of T cell receptor (TCR) signaling and provides a means of amplifying T cell effector responses in an antigen-nonspecific manner. While the role of Programmed Cell Death Protein 1 (PD-1) on antigen-specific T cell responses is extensively characterized, its role in bystander T cell responses is less clear. We examined the role of the PD-1 pathway during human and mouse non–antigen-specific memory T cell bystander activation and observed that PD-1+ T cells demonstrated less activation and proliferation than activated PD-1 populations in vitro. Higher activation and proliferative responses were also observed in the PD-1 memory population in both mice and patients with cancer receiving high-dose IL-2, mirroring the in vitro phenotypes. This inhibitory effect of PD-1 could be reversed by PD-1 blockade in vivo or observed using memory T cells from PD-1–/– mice. Interestingly, increased activation through abrogation of PD-1 signaling in bystander-activated T cells also resulted in increased apoptosis due to activation-induced cell death (AICD) and eventual T cell loss in vivo. These results demonstrate that the PD-1/PD-Ligand 1 (PD-L1) pathway inhibited bystander-activated memory T cell responses but also protected cells from AICD.

Original languageEnglish (US)
Article numbere173287
JournalJCI Insight
Issue number18
StatePublished - 2023

Bibliographical note

Publisher Copyright:
© 2023, Le et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Regulation of human and mouse bystander T cell activation responses by PD-1'. Together they form a unique fingerprint.

Cite this