ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2014
T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model.
Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- A stage-based framework to interpret regulatory T cell biology after heart transplantation.Frontiers in cardiovascular medicine · 2026Review
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Tolerogenic Therapies in Cardiac Transplantation.International journal of molecular sciences · 2025Review
- Animal models for transplant immunology: bridging bench to bedside.Clinical transplantation and research · 2024Review
- A heart transplant center experience with basiliximab induction strategies: A double edged sword?Clinical transplantation · 2024Article
- Targeting inflammation and immune activation to improve CTLA4-Ig-based modulation of transplant rejection.Frontiers in immunology · 2022Review
- Creation of human hematopoietic chimeric cell (HHCC) line as a novel strategy for tolerance induction in transplantation.Stem cell investigation · 2022Article
- Everolimus-Induced Immune Effects after Heart Transplantation: A Possible Tool for Clinicians to Monitor Patients at Risk for Transplant Rejection.Life (Basel, Switzerland) · 2021Article
- Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance.The Journal of clinical investigation · 2021Article
- Investigation of hub genes and immune status in heart transplant rejection using endomyocardial biopsies.Journal of cellular and molecular medicine · 2021Article
- Treg Therapies Revisited: Tolerance Beyond Deletion.Frontiers in immunology · 2020Review
- A Prospective Controlled Trial to Evaluate Safety and Efficacy ofFrontiers in medicine · 2020Article
- Hurdles to Cardioprotection in the Critically Ill.International journal of molecular sciences · 2019Review
- Treg-mediated prolonged survival of skin allografts without immunosuppression.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Induction of Tolerance Towards Solid Organ Allografts Using Hematopoietic Cell Transplantation in Large Animal Models.OBM transplantation · 2019Article
- CTLA4Ig Improves Murine iTreg Induction via TGFJournal of immunology research · 2018Article
- Regulatory Role of CD4Journal of immunology research · 2018Review
- Murine models of transplantation tolerance through mixed chimerism: advances and roadblocks.Clinical and experimental immunology · 2017Review
- Effect of Ex Vivo-Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques.Transplantation · 2017Article
- Anti-Interleukin-6 Promotes Allogeneic Bone Marrow Engraftment and Prolonged Graft Survival in an Irradiation-Free Murine Transplant Model.Frontiers in immunology · 2017Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe mixed chimerism approach induces donor-specific tolerance in both pre-clinical models and clinical pilot trials. However, chronic rejection of heart allografts and acute rejection of skin allografts were observed in some chimeric animals despite persistent hematopoietic chimerism and tolerance toward donor antigens in vitro. We tested whether additional cell therapy with regulatory T cells (Tregs) is able to induce full immunologic tolerance and prevent chronic rejection.
methodsWe recently developed a murine "Treg bone marrow (BM) transplantation (BMT) protocol" that is devoid of cytoreductive recipient pre-treatment. The protocol consists of a moderate dose of fully mismatched allogeneic donor BM under costimulation blockade, together with polyclonal recipient Tregs and rapamycin. Control groups received BMT under non-myeloablative irradiation and costimulation blockade without Treg therapy. Multilineage chimerism was followed by flow cytometry, and tolerance was assessed by donor-specific skin and heart allografts.
resultsDurable multilineage chimerism and long-term donor skin and heart allograft survival were successfully achieved with both protocols. Notably, histologic examination of heart allografts at the end of follow-up revealed that chronic rejection is prevented only in chimeras induced with the Treg protocol.
conclusionsIn a mouse model of mixed chimerism, additional Treg treatment at the time of BMT prevents chronic rejection of heart allografts. As the Treg-chimerism protocol also obviates the need for cytoreductive recipient treatment it improves both efficacy and safety over previous non-myeloablative mixed chimerism regimens. These results may significantly impact the development of protocols for tolerance induction in cardiac transplantation.
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