ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2012
Integrin antagonists prevent costimulatory blockade-resistant transplant rejection by CD8(+) memory T cells.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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
47 citing papers in PubMed.
- New Immunosuppressants in Pediatric Kidney Transplantation: What's in the Pipeline for Kids?Pediatric transplantation · 2025Review
- Costimulatory Blockade and Solid Organ Transplantation: The Past, Present, and Future.Kidney international reports · 2023Review
- Activation and regulation of alloreactive T cell immunity in solid organ transplantation.Nature reviews. Nephrology · 2022Review
- Targeting inflammation and immune activation to improve CTLA4-Ig-based modulation of transplant rejection.Frontiers in immunology · 2022Review
- TIGIT regulates apoptosis of risky memory T cell subsets implicated in belatacept-resistant rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Memory T Cells in Transplantation: Old Challenges Define New Directions.Transplantation · 2020Review
- Memory T cell-mediated rejection is mitigated by FcγRIIB expression on CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Costimulation Blockade in Vascularized Composite Allotransplantation.Frontiers in immunology · 2020Review
- 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
- Characterization of eomesodermin and T-bet expression by allostimulated CD8Clinical and experimental immunology · 2018Article
- Four-Dimensional Imaging of T Cells in Kidney Transplant Rejection.Journal of the American Society of Nephrology : JASN · 2018Article
- Selective CD28 blockade attenuates CTLA-4-dependent CD8+ memory T cell effector function and prolongs graft survival.JCI insight · 2018Article
- LFA-1 in T Cell Migration and Differentiation.Frontiers in immunology · 2018Review
- 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
- CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients.JCI insight · 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
- Interruption of OX40L signaling prevents costimulation blockade-resistant allograft rejection.JCI insight · 2017Article
- Advances in targeting co-inhibitory and co-stimulatory pathways in transplantation settings: the Yin to the Yang of cancer immunotherapy.Immunological reviews · 2017Review
- Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation.Frontiers in immunology · 2017Review
- Role of Memory T Cells in Allograft Rejection and Tolerance.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The success of belatacept in late-stage clinical trials inaugurates the arrival of a new class of immunosuppressants based on costimulatory blockade, an immunosuppression strategy that disrupts essential signals required for alloreactive T-cell activation. Despite having improved renal function, kidney transplant recipients treated with belatacept experienced increased rates of acute rejection. This finding has renewed focus on costimulatory blockade-resistant rejection and specifically the role of alloreactive memory T cells in mediating this resistance. To study the mechanisms of costimulatory blockade-resistant rejection and enhance the clinical efficacy of costimulatory blockade, we developed an experimental transplant system that models a donor-specific memory CD8(+) T-cell response. After confirming that graft-specific memory T cells mediate costimulatory blockade-resistant rejection, we characterized the role of integrins in this rejection. The resistance of memory T cells to costimulatory blockade was abrogated when costimulatory blockade was coupled with either anti-VLA-4 or anti-LFA-1. Mechanistic studies revealed that in the presence of costimulatory blockade, anti-VLA-4 impaired T-cell trafficking to the graft but not memory T-cell recall effector function, whereas anti-LFA-1 attenuated both trafficking and memory recall effector function. As antagonists against these integrins are clinically approved, these findings may have significant translational potential for future clinical transplant trials.
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