ArticleJournal of thrombosis and haemostasis : JTH2020
Antigen-specific in vitro expansion of factor VIII-specific regulatory T cells induces tolerance in hemophilia A mice.
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Clinical progress of engineered cellular immunotherapies for autoimmunity.Nature biotechnology · 2026Review
- The T follicular helper/T follicular helper regulatory pathway in FVIII immune responses in mice.Blood · 2025Article
- Transplanted gene-modified placental cells boost FVIII activity in pediatric sheep without eliciting immunity, toxicity, or adverse events.Frontiers in immunology · 2025Article
- Non-viral and viral delivery systems for hemophilia A therapy: recent development and prospects.Annals of hematology · 2024Review
- Immune tolerance against infused FVIII in hemophilia A is mediated by PD-L1+ Tregs.The Journal of clinical investigation · 2022Article
- CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications.Biomedicines · 2022Review
- Regulatory CAR-T cells in autoimmune diseases: Progress and current challenges.Frontiers in immunology · 2022Review
- Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells.Molecular therapy. Methods & clinical development · 2021Article
- Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy?Gene therapy · 2021Review
- CD4Cellular immunology · 2020Article
- A Treg-Selective IL-2 Mutein Prevents the Formation of Factor VIII Inhibitors in Hemophilia Mice Treated With Factor VIII Gene Therapy.Frontiers in immunology · 2020Article
- Escape or Fight: Inhibitors in Hemophilia A.Frontiers in immunology · 2020Review
- Tolerating Factor VIII: Recent Progress.Frontiers in immunology · 2019Review
- Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFollowing protein replacement therapy, one-third of severe hemophilia A patients develop antibodies to factor VIII (FVIII), which also hinders the efficacy of gene therapy. Regulatory T cells (Tregs) have a naturally suppressive function that potentially reduces the immune response to FVIII therapy. Furthermore, antigen-specific Tregs are functionally much more potent than polyclonal cells. Adoptive transfer of antigen-specific Tregs can effectively suppress anti-FVIII antibody responses.
objectiveDevelop a clinically feasible protocol to enrich and expand Tregs specific to FVIII for suppressing anti-FVIII immune responses.
methodsRegulatory T cells are isolated from FVIII-sensitized mice, sorted on CD25
resultsIn vitro FVIII-specific suppressive assays indicate that FVIII specifically expanded Tregs are more suppressive than non-specifically expanded and naive Tregs. Adoptive transfer of expanded Tregs into HemA mice showed that FVIII-specifically expanded Tregs are significantly more potent in suppressing anti-FVIII immune responses in FVIII plasmid-treated HemA mice. Moreover, the FVIII-specific immune tolerance is maintained after a secondary challenge with FVIII plasmid.
conclusionsOur results demonstrate that the FVIII-specific sensitization and expansion protocol yields more potent Tregs to suppress anti-FVIII antibody responses and induce long-term tolerance to FVIII, increasing the potential for adoptive Treg cell therapy to modulate anti-FVIII immune responses.
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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.