CD8 regulatory T cells are a novel type regulatory T cells in the induction of transplantation immune tolerance

By
Jin-can Huang
Yang Zhao
Yu-di Han
Zheng Xia
Guo-sheng Du
Ren Lang
Lin Zhou

May 5, 2026

Frontiers In Immunology

Overview

This study identifies CD8+CD45RClow/- regulatory T cells (Tregs) as significant contributors to immune tolerance in liver transplantation. Their presence correlates with long-term stable graft function, suggesting a potential role in modulating immune responses.

Background

Understanding the mechanisms of immune tolerance in transplantation is critical for improving graft survival and reducing reliance on immunosuppressive therapies. While CD4+ Tregs have been extensively studied, the emerging role of CD8+ Tregs in promoting tolerance is less understood. This research highlights the importance of CD8+ Treg subsets in achieving and maintaining transplant tolerance.

Data Highlights

Finding	Details
Graft Longevity	Adoptive transfer of tolDCs extended graft longevity in rat models.
Treg Levels	Increased levels of CD4+Foxp3+ and CD8+CD45RClow/- Tregs were found in tolerant subjects.
Concentration in Grafts	MHC-II+CD8+CD45RClow/- Tregs were concentrated in tolerant grafts.
Clinical Correlation	Higher prevalence of CD8+CD45RClow/- Tregs in liver transplant recipients with stable graft function.

Key Findings

CD8+CD45RClow/- Tregs are linked to immune tolerance in transplantation.
Adoptive transfer of tolerogenic dendritic cells (tolDCs) improves graft longevity.
Elevated levels of both CD4+Foxp3+ and CD8+CD45RClow/- Tregs were observed in tolerant subjects.
MHC-II+CD8+CD45RClow/- Tregs are concentrated in tolerant grafts, indicating local immune modulation.
Higher prevalence of CD8+CD45RClow/- Tregs in recipients with long-term stable graft function compared to those with acute rejection.

Clinical Implications

The findings suggest that enhancing CD8+ Treg populations may be a viable strategy for promoting transplant tolerance and reducing the need for immunosuppressive therapy. Clinicians should consider the potential role of CD8+ Tregs in monitoring graft function and developing tolerance-inducing therapies.

Conclusion

CD8+CD45RClow/- Tregs play a critical role in transplant immune tolerance and may work in conjunction with CD4+Foxp3+ Tregs to maintain a tolerant immune environment. Further research is warranted to explore their therapeutic potential.