Regulatory T cell therapy and immune tolerance in heart transplantation: a translational evidence framework for regulatory T cells-cell characterization and recipient-graft monitoring
Abstract
Regulatory T cell (Treg) therapy is a candidate strategy for improving donor-specific immune regulation after heart transplantation and, in the long term, may reduce reliance on lifelong immunosuppression. This Review separates mechanistic and preclinical evidence from human case observations, prospective clinical-trial protocols, manufacturing studies, and translational hypotheses. We summarize pathways that support Treg function in experimental transplantation and evaluate context-dependent outputs, including amphiregulin and CXCL15-related signaling, as potential safety signals rather than validated clinical biomarkers. We then compare peripheral-blood-derived and thymus-derived Treg-cell preparations, focusing on source material, manufacturing, cryopreservation, cell identity and potency, and infusion timing. Human evidence for Thy-Tregs in heart transplantation includes one fully reported index case and preliminary, incompletely reported data on the first four THYTECH recipients. ATT-Heart provides a prospective phase I evaluation framework. Finally, we assess allogeneic Thy-Treg banks, thymic organoids, and thymic transplantation as exploratory routes for adult recipients. The central translational question is whether a defined Treg-cell therapy can persist, remain functionally stable, and be monitored safely in the inflammatory environment of cardiac transplantation.
Related
- TIGIT+ B cells: emerging immunoregulatory players in autoimmunity and transplantation tolerance with therapeutic potential
- Halophyte-associated salt-tolerant rhizobacteria: ecological adaptation, mechanistic pathways, and translational relevance for wheat salinity tolerance
- Ion regulatory mechanisms supporting hypersaline tolerance in the coastal rock pool mosquito Aedes togoi
- Syngeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide to induce immune tolerance of allogenic skin graft survival in rat.
- Cis-regulatory inactivation of vitamin D signaling confers extreme calcium tolerance in Jialing fish
BibTeX
@article{zhaotong2026regulatory,
title = {{Regulatory T cell therapy and immune tolerance in heart transplantation: a translational evidence framework for regulatory T cells-cell characterization and recipient-graft monitoring}},
author = {Gong Zhaotong and Liu Yizhang and Li Linke},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1977203},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977203},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Regulatory T cell therapy and immune tolerance in heart transplantation: a translational evidence framework for regulatory T cells-cell characterization and recipient-graft monitoring
AU - Gong Zhaotong
AU - Liu Yizhang
AU - Li Linke
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1977203
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977203
AB - Regulatory T cell (Treg) therapy is a candidate strategy for improving donor-specific immune regulation after heart transplantation and, in the long term, may reduce reliance on lifelong immunosuppression. This Review separates mechanistic and preclinical evidence from human case observations, prospective clinical-trial protocols, manufacturing studies, and translational hypotheses. We summarize pathways that support Treg function in experimental transplantation and evaluate context-dependent outputs, including amphiregulin and CXCL15-related signaling, as potential safety signals rather than validated clinical biomarkers. We then compare peripheral-blood-derived and thymus-derived Treg-cell preparations, focusing on source material, manufacturing, cryopreservation, cell identity and potency, and infusion timing. Human evidence for Thy-Tregs in heart transplantation includes one fully reported index case and preliminary, incompletely reported data on the first four THYTECH recipients. ATT-Heart provides a prospective phase I evaluation framework. Finally, we assess allogeneic Thy-Treg banks, thymic organoids, and thymic transplantation as exploratory routes for adult recipients. The central translational question is whether a defined Treg-cell therapy can persist, remain functionally stable, and be monitored safely in the inflammatory environment of cardiac transplantation.
SN - 1664-3224
ER -