ArticleBlood2016
Programming of donor T cells using allogeneic δ-like ligand 4-positive dendritic cells to reduce GVHD in mice.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation.The Journal of experimental medicine · 2025Article
- Notch Signaling Regulates the Function and Phenotype of Dendritic Cells inMicroorganisms · 2023Article
- Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants.Science advances · 2021Article
- Alloantigen-activated (AAA) CD4Journal of experimental & clinical cancer research : CR · 2021Article
- Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants.bioRxiv : the preprint server for biology · 2021Article
- Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.bioRxiv : the preprint server for biology · 2021Article
- Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.Science advances · 2021Article
- Current Views on the Roles ofBiomolecules · 2021Review
- Graft-versus-host disease depletes plasmacytoid dendritic cell progenitors to impair tolerance induction.The Journal of clinical investigation · 2021Article
- Child with Wiskott-Aldrich syndrome underwent atypical immune reconstruction after umbilical cord blood transplantation: A case report.World journal of clinical cases · 2019Article
- Dendritic Cell Regulation of Graft-Vs.-Host Disease: Immunostimulation and Tolerance.Frontiers in immunology · 2019Review
- AAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2018Article
- Bone marrow transplant-induced alterations in Notch signaling promote pathologic Th17 responses to γ-herpesvirus infection.Mucosal immunology · 2018Article
- A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy.Journal of hematology & oncology · 2017Review
- Notch Signaling and Immune Regulation in Alloimmunity.Current transplantation reports · 2016Article
- DLL4Pharmacological research · 2016Review
- Epigenetic Regulation of Dendritic Cell Development and Function.Cancer journal (Sudbury, Mass.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 9 institutions in 3 countries.
Funding
Abstract
Alloreactive T cells play a critical role in eliminating hematopoietic malignant cells but are also the mediators of graft-versus-host disease (GVHD), a major complication that subverts the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, induction of alloreactive T cells does not necessarily lead to GVHD. Here we report the development of a cellular programming approach to render alloreactive T cells incapable of causing severe GVHD in both major histocompatibility complex (MHC)-mismatched and MHC-identical but minor histocompatibility antigen-mismatched mouse models. We established a novel platform that produced δ-like ligand 4-positive dendritic cells (Dll4(hi)DCs) from murine bone marrow using Flt3 ligand and Toll-like receptor agonists. Upon allogeneic Dll4(hi)DC stimulation, CD4(+) naïve T cells underwent effector differentiation and produced high levels of interferon γ (IFN-γ) and interleukin-17 in vitro, depending on Dll4 activation of Notch signaling. Following transfer, allogeneic Dll4(hi)DC-induced T cells were unable to mediate severe GVHD but preserved antileukemic activity, significantly improving the survival of leukemic mice undergoing allogeneic HSCT. This effect of Dll4(hi)DC-induced T cells was associated with their impaired expansion in GVHD target tissues. IFN-γ was important for Dll4(hi)DC programming to reduce GVHD toxicities of alloreactive T cells. Absence of T-cell IFN-γ led to improved survival and expansion of Dll4(hi)DC-induced CD4(+) T cells in transplant recipients and caused lethal GVHD. Our findings demonstrate that Dll4(hi)DC programming can overcome GVHD toxicity of donor T cells and produce leukemia-reactive T cells for effective immunotherapy.
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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.