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September 19, 2020Biology of Blood and Marrow TransplantationOpen Access

Clinical-Grade Expanded Regulatory T Cells Are Enriched with Highly Suppressive Cells Producing IL-10, Granzyme B, and IL-35

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Authors

FUFrancesca UlbarIVIda VillanovaRGRaffaella Giancola

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Overview

Preclinical study demonstrates automated expansion produces potent regulatory T cells in mouse models, highlighting a viable strategy to prevent graft-versus-host disease.

Key Points

  • To evaluate an automated, clinical-grade protocol for the expansion and functional enhancement of regulatory T cells to prevent graft-versus-host disease in mismatched transplantation.
  • Purified CD4+CD25+ regulatory T cells via CliniMACS and expanded 100 × 10^6 cells for 14 days using the automated CliniMACS Prodigy System.
  • Characterized phenotype, cytokine expression, and suppressive capacity in vitro by flow cytometry, cell sorting, and mRNA quantification.
  • Tested in vivo efficacy against graft-versus-host disease (GVHD) in an NSG mouse model co-infused with conventional T cells.
  • Culture expanded starting cells to 684 ± 279 × 10^6, increasing FoxP3+ purity (82 ± 8%), suppressive activity (75 ± 12%), and marker expression for CD39 (58.1 ± 13.3%, P < .05), CTLA4 (85.4 ± 9.8%, P < .01), and TIM3 (29 ± 16%, P < .05).
  • Analysis demonstrated significant upregulation of CD39, IL-10, granzyme B, and IL-35 mRNA (P < .05), with isolated TIM3+ populations showing highest IL-10 and granzyme B levels (P < .01).
  • Mice receiving conventional T cells alone died of GVHD, whereas mice co-infused with expanded regulatory T cells survived without GVHD.

Cite This Study

Ulbar et al. (2020) studied this question.

synapsesocial.com/papers/6a6f57e3a528af2d65c2f1behttps://doi.org/10.1016/j.bbmt.2020.08.034
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1CD25+CD27+CD70− alloantigen-specific Tregs: promising stable immunotherapy for transplantation2026
  2. 2Increased Suppressor Activity of Ex Vivo Transformed Regulatory T Cells in Comparison with Unstimulated Cells of the Same Donor2022 · 1 citations
  3. 3Overexpression of CD103 on regulatory T cells mitigates acute graft-versus-host disease via promotion of tolerogenic dendritic cell networks2025 · 1 citations
  4. 4Experience in manufacturing a haploidentical biomedical cell product enriched with regulatory T-lymphocytes2024
  5. 5Stable and Functional Regulatory T Cells for Adoptive Cell Therapy2026