ArticleThe Journal of experimental medicine2008
A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01163799 (A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients), which is not on this map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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.
A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients
Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 302 citations in OpenAlex.
- Pooled it
- The ratio of circulating regulatory T cells (Tregs)/Th17 cells is associated with acute allograft rejection in liver transplantation.PloS one · 2014Trial
- Single-cell and spatial transcriptomics identify immune-stromal interactions in cardiac allograft vasculopathy.Nature cardiovascular research · 2026Article
- How Cytokines Regulate Immune Response Toward Chronic Allograft Rejection?Results and problems in cell differentiation · 2026Review
- Epigenetic regulation in transplant rejection and tolerance: mechanisms and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- Heart Transplantation: Immunological Challenges Revisited.Current cardiology reviews · 2026Review
- Intestinal reengineering: Scientific advances in intestinal transplantation.World journal of gastrointestinal surgery · 2025Review
- Best practices of heart transplantation in mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Protective effects of an Fc-engineered PD-L1 fusion protein in a spontaneous abortion model and a Th17 cell-induced pregnancy loss model.Frontiers in pharmacology · 2025Article
- Animal models for transplant immunology: bridging bench to bedside.Clinical transplantation and research · 2024Review
- Targeting T helper 17 cells: emerging strategies for overcoming transplant rejection.Clinical transplantation and research · 2024Review
- Dysregulated Treg repair responses lead to chronic rejection after heart transplantation.The Journal of clinical investigation · 2024Article
- Article
- RORγt inverse agonist TF-S14 inhibits Th17 cytokines and prolongs skin allograft survival in sensitized mice.Communications biology · 2024Article
- Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation.Frontiers in immunology · 2024Article
- Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants.Frontiers in immunology · 2024Article
- The Functional Adaptability of Hyporesponsive T Cells and its Impact on Transplant Outcomes.Current transplantation reports · 2023Article
- New insights into maladaptive vascular responses to donor specific HLA antibodies in organ transplantation.Frontiers in transplantation · 2023Review
- The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses.International journal of molecular sciences · 2022Review
- Immunogenetic Role of IL17A Polymorphism in the Pathogenesis of Recurrent Miscarriage.Journal of clinical medicine · 2022Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
T-bet plays a crucial role in Th1 development. We investigated the role of T-bet in the development of allograft rejection in an established MHC class II-mismatched (bm12 into B6) model of chronic allograft vasculopathy (CAV). Intriguingly, and in contrast to IFN-gamma(-/-) mice that are protected from CAV, T-bet(-/-) recipients develop markedly accelerated allograft rejection accompanied by early severe vascular inflammation and vasculopathy, and infiltration by predominantly IL-17-producing CD4 T cells. Concurrently, T-bet(-/-) mice exhibit a T helper type 1 (Th1)-deficient environment characterized by profound IFN-gamma deficiency, a Th2 switch characterized by increased production of interleukin (IL) 4, IL-5, IL-10, and IL-13 cytokines, as well as increased production of the proinflammatory cytokines IL-6, IL-12p40, and IL-17. Neutralization of IL-17 inhibits accelerated allograft rejection and vasculopathy in T-bet(-/-) mice. Interestingly, CD4 but not CD8 T cell deficiency in T-bet(-/-) mice affords dramatic protection from vasculopathy and facilitates long-term graft acceptance. This is the first study establishing that in the absence of Th1-mediated alloimmune responses, CD4 Th17 cells mediate an aggressive proinflammatory response culminating in severe accelerated allograft rejection and vasculopathy. These results have important implications for the development of novel therapies to target this intractable problem in clinical solid organ transplantation.
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What OpenQuestion holds
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.