ArticleThe Journal of clinical investigation2017
PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 101 citations in OpenAlex.
- Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Prognostic values of increased B7 family proteins in haploidentical hematopoietic stem cell transplantation patients with aGVHD.International journal of hematology · 2019Trial
- GZMK-expressing tissue-resident memory CD8+ T cells participate in human intestinal acute graft-versus-host disease.JCI insight · 2026Article
- The impact of T cell exhaustion in hematopoietic stem cell transplantation.Stem cell research & therapy · 2026Review
- [The influence of different collagenases on the analysis of immune cells in salivary glands of mice with chronic graft-versus-host disease].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- The dual role of T cells in solid organ transplant rejection and immune tolerance.Frontiers in immunology · 2026Review
- T cell-macrophage crosstalk in GVHD and cancer immunotherapy.Cell investigation · 2025Article
- PD-1 inhibition for relapse after allogeneic transplantation in acute myeloid leukemia and myelodysplastic syndrome.Blood advances · 2025Article
- IFN-γ and donor leukocyte infusions for relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation.JCI insight · 2025Article
- Enhance the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells in prevention of acute graft-versus-host disease through CRISPLD2 modulation.Stem cell research & therapy · 2025Article
- Allogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD.Journal of experimental & clinical cancer research : CR · 2025Article
- Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Anti-CD4 monoclonal antibody prevents chronic graft-versus-host disease in mice by inducing immune tolerance of CD8Frontiers in immunology · 2024Article
- Genetic and pharmaceutical targeting of HIF1α allows combo-immunotherapy to boost graft vs. leukemia without exacerbation graft vs. host disease.Cell reports. Medicine · 2023Article
- The opposite impact of Janus kinase inhibitor Ruxolitinib on the function of bone marrow mesenchymal stem cells and immune cells in acute GVHD recipients.Blood science (Baltimore, Md.) · 2023Article
- Defining a TCF1-expressing progenitor allogeneic CD8Nature communications · 2023Article
- Graft conditioning with fluticasone propionate reduces graft-versus-host disease upon allogeneic hematopoietic cell transplantation in mice.EMBO molecular medicine · 2023Article
- Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
- Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and the immunostimulatory molecule CD80 and functions as a checkpoint to regulate immune responses. The interaction of PD-L1 with CD80 alone has been shown to exacerbate the severity of graft-versus-host disease (GVHD), whereas costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that temporary depletion of donor CD4+ T cells early after hematopoietic cell transplantation effectively prevents GVHD while preserving strong graft-versus-leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models. Depletion of donor CD4+ T cells increased serum IFN-γ but reduced IL-2 concentrations, leading to upregulation of PD-L1 expression by recipient tissues and donor CD8+ T cells. In GVHD target tissues, the interactions of PD-L1 with PD-1 on donor CD8+ T cells cause anergy, exhaustion, and apoptosis, thereby preventing GVHD. In lymphoid tissues, the interactions of PD-L1 with CD80 augment CD8+ T cell expansion without increasing anergy, exhaustion, or apoptosis, resulting in strong GVL effects. These results indicate that the outcome of PD-L1-mediated signaling in CD8+ T cells depends on the presence or absence of CD4+ T cells, the nature of the interacting receptor expressed by CD8+ T cells, and the tissue environment in which the signaling occurs.
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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.