ArticleTransplantation2012
Combined costimulatory and leukocyte functional antigen-1 blockade prevents transplant rejection mediated by heterologous immune memory alloresponses.
Article in Transplantation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 27 citations in OpenAlex.
- Best practices in mouse models of skin transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Review
- Peritransplant VLA-4 blockade inhibits endogenous memory CD8 T cell infiltration into high-risk cardiac allografts and CTLA-4Ig resistant rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- T Cell Repertoire Maturation Induced by Persistent and Latent Viral Infection Is Insufficient to Induce Costimulation Blockade Resistant Organ Allograft Rejection in Mice.Frontiers in immunology · 2018Article
- Belatacept-Resistant Rejection Is Associated With CD28American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- Selective Targeting of High-Affinity LFA-1 Does Not Augment Costimulation Blockade in a Nonhuman Primate Renal Transplantation Model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- Advances in targeting co-inhibitory and co-stimulatory pathways in transplantation settings: the Yin to the Yang of cancer immunotherapy.Immunological reviews · 2017Review
- The impact of cell surface PEGylation and short-course immunotherapy on islet graft survival in an allogeneic murine model.Acta biomaterialia · 2017Article
- Successful Treatment of T Cell-Mediated Acute Rejection with Delayed CTLA4-Ig in Mice.Frontiers in immunology · 2017Article
- CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016Article
- A novel multi-parameter assay to dissect the pharmacological effects of different modes of integrin αLβ2 inhibition in whole blood.British journal of pharmacology · 2015Article
- Viral-induced CD28 loss evokes costimulation independent alloimmunity.The Journal of surgical research · 2015Article
- Multipotent mesenchymal stromal cells synergize with costimulation blockade in the inhibition of immune responses and the induction of Foxp3+ regulatory T cells.Stem cells translational medicine · 2014Article
- Experimental models of cardiac transplantation: design determines relevance.Current opinion in organ transplantation · 2014Review
- T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2014Article
- Endogenous memory CD8 T cells directly mediate cardiac allograft rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Article
- Targeting co-stimulatory pathways: transplantation and autoimmunity.Nature reviews. Nephrology · 2014Review
- Endogenous memory CD8 T cells are activated within cardiac allografts without mediating rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2013Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRecent evidence suggests that alloreactive memory T cells are generated by the process of heterologous immunity, whereby memory T cells arising in response to pathogen infection crossreact with donor antigens. Because of their diminished requirements for costimulation during recall, these pathogen-elicited allocrossreactive memory T cells are of particular clinical importance, especially given the emergence of costimulatory blockade as a transplant immunosuppression strategy.
methodsWe used an established model of heterologous immunity involving sequential infection of a naïve C57BL/6 recipient with lymphocytic choriomeningitis virus and vaccinia virus, followed by combined skin and bone marrow transplant from a BALB/c donor.
resultsWe demonstrate that coupling the integrin antagonist anti-leukocyte functional antigen (LFA)-1 with costimulatory blockade could surmount the barrier posed by heterologous immunity in a fully allogeneic murine transplant system. The combined costimulatory and integrin blockade regimen suppressed proliferation of alloreactive memory T cells and attenuated their cytokine effector responses. This combined blockade regimen also promoted the retention of FoxP³⁺ Tregs in draining lymph nodes. Finally, we show that in an in vitro mixed lymphocyte reaction system using human T cells, the combination of belatacept and anti-LFA-1 was able to suppress cytokine production by alloreactive memory T cells that was resistant to belatacept alone.
conclusionsAs an antagonist against human LFA-1 exists and has been used clinically to treat psoriasis, these findings have significant translational potential for future clinical transplant trials.
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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.