ArticleJournal of immunology (Baltimore, Md. : 1950)2015
HY-Specific Induced Regulatory T Cells Display High Specificity and Efficacy in the Prevention of Acute Graft-versus-Host Disease.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- G-CSF-induced macrophage polarization and mobilization may prevent acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.Bone marrow transplantation · 2019Trial
- Selection and Characterisation of Minor Histocompatibility Antigen-Specific Regulatory T Cells in Fully HLA-Matched Setting for GVHD Therapy.European journal of immunology · 2025Article
- Immune isolation-enabled nanoencapsulation of donor T cells: a promising strategy for mitigating GVHD and treating AML in preclinical models.Journal for immunotherapy of cancer · 2024Article
- The impact of regulatory T cells on the graft-versus-leukemia effect.Frontiers in immunology · 2024Review
- Review
- Sex as a biological variable: Mechanistic insights and clinical relevance in solid organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Review
- The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease.The Journal of clinical investigation · 2022Article
- Emerging translational strategies and challenges for enhancing regulatory T cell therapy for graft-versus-host disease.Frontiers in immunology · 2022Review
- First-in-human phase 1 trial of induced regulatory T cells for graft-versus-host disease prophylaxis in HLA-matched siblings.Blood advances · 2021Article
- Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD.Nature reviews. Clinical oncology · 2020Review
- Bone Marrow Transplantation Platform to Investigate the Role of Dendritic Cells in Graft-versus-Host Disease.Journal of visualized experiments : JoVE · 2020Article
- Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications.Frontiers in immunology · 2020Review
- Early myeloid-derived suppressor cells (HLA-DRJournal of hematology & oncology · 2019Article
- Achievement of Tolerance Induction to Prevent Acute Graft-vs.-Host Disease.Frontiers in immunology · 2019Review
- Foxp3 Instability Helps tTregs Distinguish Self and Non-self.Frontiers in immunology · 2019Review
- A Phase I Clinical Trial with Ex Vivo Expanded Recipient Regulatory T cells in Living Donor Kidney Transplants.Scientific reports · 2018Article
- Strategies for Enhancing and Preserving Anti-leukemia Effects Without Aggravating Graft-Versus-Host Disease.Frontiers in immunology · 2018Review
- CD8(+) Tregs promote GVHD prevention and overcome the impaired GVL effect mediated by CD4(+) Tregs in mice.Oncoimmunology · 2016Article
- Regulatory T-Cell Therapy for Graft-versus-host Disease.Journal of immunology research and therapy · 2016Article
- Article
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Authors and funding
8 authors.
Funding
Abstract
Naturally derived regulatory T cells (Tregs) may prevent graft-versus-host disease (GVHD) while preserving graft-versus-leukemia (GVL) activity. However, clinical application of naturally derived regulatory T cells has been severely hampered by their scarce availability and nonselectivity. To overcome these limitations, we took alternative approaches to generate Ag-specific induced Tregs (iTregs) and tested their efficacy and selectivity in the prevention of GVHD in preclinical models of bone marrow transplantation. We selected HY as a target Ag because it is a naturally processed, ubiquitously expressed minor histocompatibility Ag (miHAg) with a proven role in GVHD and GVL effect. We generated HY-specific iTregs (HY-iTregs) from resting CD4 T cells derived from TCR transgenic mice, in which CD4 cells specifically recognize HY peptide. We found that HY-iTregs were highly effective in preventing GVHD in male (HY(+)) but not female (HY(-)) recipients using MHC II-mismatched, parent→F1, and miHAg-mismatched murine bone marrow transplantation models. Interestingly, the expression of target Ag (HY) on the hematopoietic or nonhematopoietic compartment alone was sufficient for iTregs to prevent GVHD. Furthermore, treatment with HY-iTregs still preserved the GVL effect even against pre-established leukemia. We found that HY-iTregs were more stable in male than in female recipients. Furthermore, HY-iTregs expanded extensively in male but not female recipients, which in turn significantly reduced donor effector T cell expansion, activation, and migration into GVHD target organs, resulting in effective prevention of GVHD. This study demonstrates that iTregs specific for HY miHAgs are highly effective in controlling GVHD in an Ag-dependent manner while sparing the GVL effect.
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Registered trials
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