ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2016
Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Transient prophylactic immunosuppression with abatacept or dasatinib prevents immune responses in AAV gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- CAR Treg synergy with anti-CD154 promotes infectious tolerance and dictates allogeneic heart transplant acceptance.JCI insight · 2025Article
- Immunosuppression Management in Heart Transplantation.Methodist DeBakey cardiovascular journal · 2025Review
- Belatacept inhibit human B cell germinal center development in immunodeficient mice.Scientific reports · 2023Article
- From bench to bedside: reversing established antibody responses and desensitization.Current opinion in organ transplantation · 2022Review
- Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept.Frontiers in immunology · 2022Article
- Harnessing the B Cell Response in Kidney Transplantation - Current State and Future Directions.Frontiers in immunology · 2022Review
- Targeting T Follicular Helper Cells to Control Humoral Allogeneic Immunity.Transplantation · 2021Review
- The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation.International journal of molecular sciences · 2021Review
- Superior inhibition of alloantibody responses with selective CD28 blockade is CTLA-4 dependent and T follicular helper cell specific.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells.Frontiers in immunology · 2021Review
- Targeting co-stimulatory molecules in autoimmune disease.Nature reviews. Drug discovery · 2020Review
- Reversing donor-specific antibody responses and antibody-mediated rejection with bortezomib and belatacept in mice and kidney transplant recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells.The Journal of clinical investigation · 2020Article
- Mechanisms of organ transplant injury mediated by B cells and antibodies: Implications for antibody-mediated rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Review
- Blockade of the costimulatory CD28-B7 family signal axis enables repeated application of AAV8 gene vectors.Journal of thrombosis and haemostasis : JTH · 2020Article
- The impact of belatacept on third-party HLA alloantibodies in highly sensitized kidney transplant recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Circulating T follicular helper cells are a biomarker of humoral alloreactivity and predict donor-specific antibody formation after transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Belatacept and CD28 Costimulation Blockade: Preventing and Reducing Alloantibodies over the Long Term.Current transplantation reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naïve T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established.
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