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

ObjectiveRegulatory T cells (Tregs) play an essential role in transplantation immune tolerance. Although CD4+ Tregs have been extensively studied, the contribution of CD8+ regulatory T-cell subsets to transplant tolerance remains less well defined. This study aimed to characterize Treg subsets associated with immune tolerance in a rat liver transplantation model and in liver transplant recipients.MethodsMesenchymal stem cell-derived tolerogenic dendritic cells (tolDCs) were adoptively infused in a rat liver transplantation model. The frequencies of CD4+Foxp3+ Tregs and CD8+CD45RClow/- Tregs in peripheral blood, spleen, and graft tissue were analyzed by flow cytometry and multiplex immunofluorescence. Peripheral blood samples from liver transplant recipients with long-term stable graft function or acute rejection were also analyzed.ResultsAdoptive infusion of tolDCs significantly prolonged graft survival in the rat liver transplantation model. Increased frequencies of CD4+Foxp3+ Tregs and CD8+CD45RClow/- Tregs were observed in peripheral blood, spleen, and graft tissue in tolDC-induced and spontaneous tolerant animals. MHC-II+CD8+CD45RClow/- Tregs were enriched within tolerant grafts, suggesting an association with local immune regulation. In liver transplant recipients, the frequency of peripheral CD8+CD45RClow/- Tregs was higher in patients with long-term stable graft function than in patients with acute rejectionConclusionCD8+CD45RClow/- Tregs are associated with transplantation immune tolerance and may cooperate with CD4+Foxp3+ Tregs in maintaining a tolerant immune microenvironment.