ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Granzyme B-Mediated Activation-Induced Death of CD4+ T Cells Inhibits Murine Acute Graft-versus-Host Disease.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Reassessing granzyme B: unveiling perforin-independent versatility in immune responses and therapeutic potentials.Frontiers in immunology · 2024Review
- Murine regulatory T cells utilize granzyme B to promote tumor metastasis.Cancer immunology, immunotherapy : CII · 2023Article
- Granzyme B prevents aberrant IL-17 production and intestinal pathogenicity in CD4Mucosal immunology · 2021Article
- MyD88 Costimulation in Donor CD8Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease.Nature communications · 2020Article
- Insights into the role of the JAK/STAT signaling pathway in graft-Therapeutic advances in hematology · 2020Review
- Host-Derived Serine Protease Inhibitor 6 Provides Granzyme B-Independent Protection of Intestinal Epithelial Cells in Murine Graft-versus-Host Disease.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018Article
- Blockade of Host β2-Adrenergic Receptor Enhances Graft-versus-Tumor Effect through Modulating APCs.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Cytotoxic Pathways in Allogeneic Hematopoietic Cell Transplantation.Frontiers in immunology · 2018Review
- T Cell-Derived CD70 Delivers an Immune Checkpoint Function in Inflammatory T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Host-Derived CD70 Suppresses Murine Graft-versus-Host Disease by Limiting Donor T Cell Expansion and Effector Function.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Targeting Cytokines in GVHD Therapy.Journal of immunology research and therapy · 2017Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Granzyme B (GzmB) has previously been shown to be critical for CD8(+) T cell-mediated graft-versus-host disease (GVHD) but dispensable for GVHD mediated by CD4(+) T cells. However, previous studies used high doses of CD4(+) T cells in MHC-mismatched models that caused rapid and lethal GVHD. Because of the hyperacute lethality, it is possible that the role of GzmB was concealed by the system. Therefore, in this study, we have titrated down the T cell dose to precisely determine the contribution of GzmB in GVHD mediated by CD4(+)CD25(-) T cells. Surprisingly, we have found that GzmB(-/-)CD4(+)CD25(-) T cells cause more severe GVHD compared with wild-type CD4(+)CD25(-) T cells in both MHC-matched and mismatched models. Mechanistic analyses reveal that although GzmB does not affect donor T cell engraftment, proliferation or tissue-specific migration, GzmB(-/-) CD4(+)CD25(-) T cells exhibit significantly enhanced expansion because of GzmB-mediated activation-induced cell death of wild-type CD4(+)CD25(-) T cells. As a result of enhanced expansion, GzmB(-/-) T cells produced higher amounts of proinflammatory cytokines (e.g., TNF-α and IFN-γ) that may contribute to the exacerbated GVHD. These results reveal that GzmB diminishes the ability of CD4(+) T cells to cause acute GVHD, which contradicts its established role in CD8(+) T cells. The differential roles suggest that targeting GzmB in selected T cell subsets may provide a strategy to control GVHD.
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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.