ArticleAnnals of surgery2002
New insights into the interactions between T-cell costimulatory blockade and conventional immunosuppressive drugs.
Article in Annals of surgery, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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Who cites it
20 citing papers in PubMed, 94 citations in OpenAlex.
- Immunomodulatory Strategies Targeting Dendritic Cells to Improve Corneal Graft Survival.Journal of clinical medicine · 2020Review
- Roles of Host Immunity in Viral Myocarditis and Dilated Cardiomyopathy.Journal of immunology research · 2018Review
- Nuclear calcium is required for human T cell activation.The Journal of cell biology · 2016Article
- T Helper Cells Fate Mapping by Co-stimulatory Molecules and its Functions in Allograft Rejection and Tolerance.International journal of organ transplantation medicine · 2014Review
- The role of costimulatory molecules in directing the functional differentiation of alloreactive T helper cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2012Review
- Implication for transglutaminase 2-mediated activation of β-catenin signaling in neointimal vascular smooth muscle cells in chronic cardiac allograft rejection.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2012Article
- The effects of Cyclosporine A and azathioprine on human T cells activated by different costimulatory signals.Immunology letters · 2011Article
- Selective CD28 blockade attenuates acute and chronic rejection of murine cardiac allografts in a CTLA-4-dependent manner.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2011Article
- Small molecule inhibition of the TNF family cytokine CD40 ligand through a subunit fracture mechanism.ACS chemical biology · 2011Article
- Rapamycin generates graft-homing murine suppressor CD8(+) T cells that confer donor-specific graft protection.Cell transplantation · 2011Article
- CCR5 blockade in combination with rapamycin prolongs cardiac allograft survival in mice.Clinical and experimental immunology · 2009Article
- Divergent role of donor dendritic cells in rejection versus tolerance of allografts.Journal of the American Society of Nephrology : JASN · 2009Article
- The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant model.The Journal of clinical investigation · 2008Article
- Transplantation tolerance: lessons from experimental rodent models.Transplant international : official journal of the European Society for Organ Transplantation · 2007Review
- Contrasting effects of cyclosporine and rapamycin in de novo generation of alloantigen-specific regulatory T cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2007Article
- Ventilator associated pneumonia and transfusion, is there really an association? (the NAVTRA study).BMC pulmonary medicine · 2006Article
- Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production.Blood · 2006Article
- Benefit-risk assessment of sirolimus in renal transplantation.Drug safety · 2005Review
- Targeting CD40L: a promising therapeutic approach.Clinical and diagnostic laboratory immunology · 2004Review
- The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity.The Journal of clinical investigation · 2003Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo determine the precise in vivo interaction between T-cell costimulatory blockade and conventional immunosuppression in transplantation. SUMMARY BACKGROUND DATA: Blocking B7 or CD154 T-cell costimulatory activation pathways prevents allograft rejection in small and large animal transplant models and is considered a promising strategy for clinical organ transplantation.
methodsA fully MHC-mismatched vascularized mouse cardiac allograft model was used to test the interactions between anti-CD154 or CTLA4Ig monotherapy and conventional immunosuppressive drugs in promoting long-term graft acceptance. The frequency of alloreactive T cell was measured by ELISPOT. Chronic rejection was examined by histology.
resultsCyclosporine, tacrolimus, and anti-IL-2R monoclonal antibody therapy abrogated the effect of a single-dose protocol of anti-CD154 therapy. In contrast, rapamycin acted synergistically with anti-CD154 therapy in promoting long-term allograft survival. The addition of calcineurin inhibitors did not abolish this synergistic effect. Intense CD154-CD40 blockade by a multiple-dose schedule of anti-CD154 resulted in long-term graft survival and profound alloreactive T-cell unresponsiveness and overcame the opposite effects of calcineurin inhibitors. CTLA4Ig induced long-term graft survival, and the effect was not affected by the concomitant use of any immunosuppressive drugs.
conclusionsThe widespread view that calcineurin inhibitors abrogate the effects of T-cell costimulatory blockade should be revisited. Sufficient costimulatory blockade and synergy induced by CD154 blockade and rapamycin promote allograft tolerance and prevent chronic rejection.
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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 Socratic graph.