ArticleBlood advances2019
Human CD8+ Tregs expressing a MHC-specific CAR display enhanced suppression of human skin rejection and GVHD in NSG mice.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 70 citations in OpenAlex.
- Review
- The Role of Chimeric Antigen Receptor Regulatory T Cells in Promoting Immune Tolerance in Solid Organ Transplantation:Saudi medical journal · 2026Review
- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- Review
- Regulatory T cell approaches for graft-versus-host disease prevention.Current opinion in immunology · 2026Review
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- CD8 regulatory T cell therapy in transplantation: a new path to clinical success?Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- Regulatory T cell therapies: biological foundations, engineering strategies, and clinical translation.Frontiers in immunology · 2026Review
- Two subsets of regulatory CD8iScience · 2025Article
- Bioengineered T-cell therapies for precision immunotherapy in renal transplantation, autoimmune relapse, and sensitization.Clinical kidney journal · 2025Review
- Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.Biomedicines · 2025Review
- Tonic signaling in CAR-T therapy: the lever long enough to move the planet.Frontiers of medicine · 2025Review
- Immunometabolism of Liver Xenotransplantation and Prospective Solutions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon.Frontiers in immunology · 2025Review
- Article
- CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.Frontiers in immunology · 2024Review
- Amyloid-β specific regulatory T cells attenuate Alzheimer's disease pathobiology in APP/PS1 mice.Molecular neurodegeneration · 2023Article
- CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential.Experimental & molecular medicine · 2023Review
- Functional heterogeneity of human skin-resident memory T cells in health and disease.Immunological reviews · 2023Review
- New cell sources for CAR-based immunotherapy.Biomarker research · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyclonal CD8+CD45RClow/- Tregs are potent regulatory cells able to control solid organ transplantation rejection and even induce tolerance. However, donor major histocompatibility complex (MHC)-specific Tregs are more potent than polyclonal Tregs in suppressing T-cell responses and preventing acute as well as chronic rejection in rodent models. The difficulty of identifying disease-relevant antigens able to stimulate Tregs has reduced the possibility of obtaining antigen-specific Tregs. To bypass this requirement and gain the advantage of antigen specificity, and thus improve the therapeutic potential of CD8+ Tregs, we stably introduced a chimeric antigen receptor (CAR) derived from a HLA-A*02 antigen-specific antibody (A2-CAR) in human CD8+ Tregs and developed a clinically compatible protocol of transduction and expansion. We demonstrated that A2-CAR CD8+ Tregs were not phenotypically altered by the process, were specifically activated, and did not exhibit cytotoxic activity toward HLA-A*02+ kidney endothelial cells (ECs). We showed that A2-CAR CD8+ Tregs were more potent suppressors of immune responses induced by HLA-A*02 mismatch than control-CAR CD8+ Tregs, both in vitro and in vivo, in models of human skin graft rejection and graft-versus-host disease (GVHD) in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. We showed that integrity of human skin graft was preserved with A2-CAR CD8+ Tregs at least 100 days in vivo after administration, and that interaction between the A2-CAR CD8+ Tregs and HLA-A*02+ kidney ECs resulted in a fine-tuned and protolerogenic activation of the ECs without cytotoxicity. Together, our results demonstrated the relevance of the CAR engineering approach to develop antigen-specific CAR-CD8+ Tregs for clinical trials in transplantation, and potentially in other diseases.
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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.