Le, Catherine T, Vick, Logan V, Collins, Craig, Dunai, Cordelia 
ORCID: 0000-0001-5799-2387, Sheng, Michael K, Khuat, Lam T, Barao, Isabel, Judge, Sean J, Aguilar, Ethan G, Curti, Brendan et al (show 6 more authors)
(2023)
Regulation of human and mouse bystander T cell activation responses by PD-1.
JCI INSIGHT, 8 (18).
e173287-.
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Animals, Humans, Mice, Cytokines, Lymphocyte Activation, Phenotype, Programmed Cell Death 1 Receptor, Memory T Cells |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 02 Feb 2024 11:40 |
| Last Modified: | 02 Feb 2024 11:40 |
| DOI: | 10.1172/jci.insight.173287 |
| Open Access URL: | https://doi.org/10.1172/jci.insight.173287 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178332 |
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