ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2011
Selective targeting of human alloresponsive CD8+ effector memory T cells based on CD2 expression.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 133 citations in OpenAlex.
- mTOR Inhibitor Therapy Diminishes Circulating CD8+ CD28- Effector Memory T Cells and Improves Allograft Inflammation in Belatacept-refractory Renal Allograft Rejection.Transplantation · 2020Trial
- Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2015Trial
- Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Trial
- Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial.Lancet (London, England) · 2011Trial
- Profiling Localized Immunomodulation and Drug Biodistribution within a Subcutaneous Vascularized Niche for Cell Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Dysfunctional decidual CD2Frontiers in immunology · 2026Article
- Second generation CD2-targeting LFA-3 fusion protein SBT115301 to restore immune homeostasis in autoimmune disease.iScience · 2025Article
- Immunotherapies for prevention and treatment of type 1 diabetes.Immunotherapy · 2025Review
- Generation and characterization of a tamoxifen-inducible lineage tracing toolFrontiers in immunology · 2025Article
- Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.Experimental & molecular medicine · 2024Review
- Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies.Frontiers in immunology · 2023Article
- Activation and regulation of alloreactive T cell immunity in solid organ transplantation.Nature reviews. Nephrology · 2022Review
- IFI16-STING-NF-κB signaling controls exogenous mitochondrion-induced endothelial activation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Modulation of Xenogeneic T-cell Proliferation by B7 and mTOR Blockade of T Cells and Porcine Endothelial Cells.Transplantation · 2022Article
- Xenotransplantation of Genetically Modified Neonatal Pig Islets Cures Diabetes in Baboons.Frontiers in immunology · 2022Article
- Polymorphic estrogen receptor binding site causes Cd2-dependent sex bias in the susceptibility to autoimmune diseases.Nature communications · 2021Article
- Endogenous memory T cells with donor-reactivity: early post-transplant mediators of acute graft injury in unsensitized recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2021Review
- Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review.World journal of transplantation · 2021Article
- Strategies for Liver Transplantation Tolerance.International journal of molecular sciences · 2021Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Costimulation blockade (CoB), specifically CD28/B7 inhibition with belatacept, is an emerging clinical replacement for calcineurin inhibitor-based immunosuppression in allotransplantation. However, there is accumulating evidence that belatacept incompletely controls alloreactive T cells that lose CD28 expression during terminal differentiation. We have recently shown that the CD2-specific fusion protein alefacept controls costimulation blockade-resistant allograft rejection in nonhuman primates. Here, we have investigated the relationship between human alloreactive T cells, costimulation blockade sensitivity and CD2 expression to determine whether these findings warrant potential clinical translation. Using polychromatic flow cytometry, we found that CD8(+) effector memory T cells are distinctly high CD2 and low CD28 expressors. Alloresponsive CD8(+) CD2(hi) CD28(-) T cells contained the highest proportion of cells with polyfunctional cytokine (IFNγ, TNF and IL-2) and cytotoxic effector molecule (CD107a and granzyme B) expression capability. Treatment with belatacept in vitro incompletely attenuated allospecific proliferation, but alefacept inhibited belatacept-resistant proliferation. These results suggest that highly alloreactive effector T cells exert their late stage functions without reliance on ongoing CD28/B7 costimulation. Their high CD2 expression increases their susceptibility to alefacept. These studies combined with in vivo nonhuman primate data provide a rationale for translation of an immunosuppression regimen pairing alefacept and belatacept to human renal transplantation.
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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.