ArticleThe Journal of clinical investigation2010
The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- The IL-10-producing NKT10 subset plays a critical role in preventing graft-versus-host-disease.Frontiers in immunology · 2026Article
- Burning Down the House: Thymic Repair and Regeneration After Acute Damage.Immunological reviews · 2025Review
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage.Immunity · 2025Article
- Anti-CD4 monoclonal antibody prevents chronic graft-versus-host disease in mice by inducing immune tolerance of CD8Frontiers in immunology · 2024Article
- Isolation of Thymus Stromal Cells from Human and Murine Tissue.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The potential role of the thymus in immunotherapies for acute myeloid leukemia.Frontiers in immunology · 2023Review
- Retention of Donor T Cells in Lymphohematopoietic Tissue and Augmentation of Tissue PD-L1 Protection for Prevention of GVHD While Preserving GVL Activity.Frontiers in immunology · 2022Review
- Review
- Article
- Current Concepts and Advances in Graft-Versus-Host Disease Immunology.Annual review of immunology · 2021Article
- Dynamics of thymus function and T cell receptor repertoire breadth in health and disease.Seminars in immunopathology · 2021Review
- Chimerism-Based Tolerance to Kidney Allografts in Humans: Novel Insights and Future Perspectives.Frontiers in immunology · 2021Review
- Murine Models Provide New Insights Into Pathogenesis of Chronic Graft-Frontiers in immunology · 2021Review
- One-two punch injury to tolerance mechanisms in graft-versus-host disease.The Journal of clinical investigation · 2020Article
- Graft-versus-host disease reduces lymph node display of tissue-restricted self-antigens and promotes autoimmunity.The Journal of clinical investigation · 2020Article
- When the Damage Is Done: Injury and Repair in Thymus Function.Frontiers in immunology · 2020Review
- T cell-derived interferon-γ programs stem cell death in immune-mediated intestinal damage.Science immunology · 2019Article
- Dendritic Cell Regulation of Graft-Vs.-Host Disease: Immunostimulation and Tolerance.Frontiers in immunology · 2019Review
- Nrf2 regulates CD4Blood · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits alphaE and beta7, CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8-like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.
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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.