ArticlePLoS biology2021
PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
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- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- Regulatory T Cells and Nanomaterials: Dual Perspectives in Therapeutics and Immunomodulation.Small science · 2026Review
- EBV Early Lytic Antigens, EBNA2 and PDL-1, in Progressive Multiple Sclerosis Brain: A Coordinated Contribution to Viral Immune Evasion.International journal of molecular sciences · 2025Article
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- Decoding the Tumor Microenvironment: Insights and New Targets from Single-Cell Sequencing and Spatial Transcriptomics.Current issues in molecular biology · 2025Review
- Programmed Death-1 Ligand 1 Domain Organization, Signaling Motifs, and Interactors in Cancer Immunotherapy.Cancers · 2025Review
- PD-L1 and FOXP3 expression in high-grade squamous intraepithelial lesions of the anogenital region.Oncotarget · 2025Article
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- Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration ofVaccines · 2025Article
- Cell-intrinsic PD-L1 signaling drives immunosuppression by myeloid-derived suppressor cells through IL-6/Jak/Stat3 in PD-L1-high lung cancer.Journal for immunotherapy of cancer · 2025Article
- Therapeutic Applications of Programmed Death Ligand 1 Inhibitors in Small Cell Lung Cancer.Biomedicines · 2025Review
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- Influence of Immune Cells and Circulating Inflammatory Cytokines on Pathological Scars: A Mendelian Randomization Study.Clinical, cosmetic and investigational dermatology · 2025Article
- Immune checkpoint inhibitor-induced thyroiditis and its potential mechanisms.Frontiers in endocrinology · 2025Review
- Discovery of a common light chain bispecific antibody targeting PD-1 and PD-L1 by Hybridoma-to-Phage-to-Yeast (H2PtY) platform.Antibody therapeutics · 2025Article
- Article
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14 authors at 4 institutions in 2 countries.
Funding
Abstract
Programmed cell death protein 1 (PD-1) is expressed on T cells upon T cell receptor (TCR) stimulation. PD-1 ligand 1 (PD-L1) is expressed in most tumor environments, and its binding to PD-1 on T cells drives them to apoptosis or into a regulatory phenotype. The fact that PD-L1 itself is also expressed on T cells upon activation has been largely neglected. Here, we demonstrate that PD-L1 ligation on human CD25-depleted CD4+ T cells, combined with CD3/TCR stimulation, induces their conversion into highly suppressive T cells. Furthermore, this effect was most prominent in memory (CD45RA-CD45RO+) T cells. PD-L1 engagement on T cells resulted in reduced ERK phosphorylation and decreased AKT/mTOR/S6 signaling. Importantly, T cells from rheumatoid arthritis patients exhibited high basal levels of phosphorylated ERK and following PD-L1 cross-linking both ERK signaling and the AKT/mTOR/S6 pathway failed to be down modulated, making them refractory to the acquisition of a regulatory phenotype. Altogether, our results suggest that PD-L1 signaling on memory T cells could play an important role in resolving inflammatory responses; maintaining a tolerogenic environment and its failure could contribute to ongoing autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.