Programmed death receptor 1 (PD-1) ligand Fc fusion proteins reduce T-cell proliferation in vitro independently of PD-1
- Author(s)
- Biemond, M; Vremec, D; Gray, DH; Hodgkin, PD; Heinzel, S;
- Details
- Publication Year 2024-12-09,Volume 102,Issue #2,Page 117-130
- Journal Title
- Immunology and Cell Biology
- Abstract
- Programmed death receptor 1 (PD-1) is an inhibitory receptor on T cells shown to restrain T-cell proliferation. PD-1 immune checkpoint blockade has emerged as a highly promising approach in cancer treatment. Much of our understanding of the function of PD-1 is derived from in vitro T-cell activation assays. Here we set out to further investigate how T cells integrate inhibitory signals such as PD-1 in vitro using the PD-1 agonist, PD-1 ligand 1 (PD-L1) fusion protein (PD-L1.Fc), coimmobilized alongside anti-CD3 agonist monoclonal antibody (mAb) on plates to deliver PD-1 signals to wild-type and PD-1(-/-) CD8(+) T cells. Surprisingly, we found that the PD-L1.Fc fusion protein inhibited T-cell proliferation independently of PD-1. This PD-L1.Fc inhibition was observed in the presence and absence of CD28 and interleukin-2 signaling. Binding of PD-L1.Fc was restricted to PD-1-expressing T cells and thus inhibition was not mediated by the interaction of PD-L1.Fc with CD80 or other yet unknown binding partners. Furthermore, a similar PD-1-independent reduction of T-cell proliferation was observed with plate-bound PD-L2.Fc. Hence, our results suggest that the coimmobilization of PD-1 ligand fusion proteins with anti-CD3 mAb leads to a reduction of T-cell engagement with plate-bound anti-CD3 mAb. This study demonstrates a nonspecific mechanism of T-cell inhibition when PD-L1.Fc or PD-L2.Fc fusion proteins are delivered in a plate-bound coimmobilization assay and highlights the importance of careful optimization of assay systems and reagents when interpreting their influence on T-cell proliferation.
- Publisher
- Wiley
- Keywords
- CD8+ T cells; Pd-1; immune checkpoints; naïve T cell activation
- Research Division(s)
- Immunology
- PubMed ID
- 38069638
- Publisher's Version
- https://doi.org/10.1111/imcb.12714
- Open Access at Publisher's Site
https://doi.org/10.1111/imcb.12714- Terms of Use/Rights Notice
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Creation Date: 2023-12-13 10:24:20
Last Modified: 2024-06-28 03:14:57