Peripheral Regulatory Cells Immunophenotyping in Kidney Transplant Recipients with Different Clinical Profiles: A Cross-Sectional Study

Abstract

Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induces peripheral tolerance. These subpopulations also might participate in maintaining allograft immunological quiescence in kidney transplant recipients (KTRs) with an excellent long-term graft function under immunosuppression (ELTGF). The aim of the study was to characterize and to enumerate peripheral Tregs, Bregs, and DCregs in KTR with an ELTGF for more than 5 years after transplant. Fourteen KTR with an ELTGF, 9 KTR with chronic graft dysfunction (CGD), and 12 healthy donors (HDs) were included in the study. CD19+-expressing peripheral B lymphocytes were purified by positive selection. IL-10-producing B cells, CD4+/CD25hi, and CD8+/CD28− Tregs, as well as CCR6+/CD123+/IDO+ DCs, were quantitated by flow cytometry. IL-10-producing Bregs (immature/transitional, but not CD19+/CD38hi/CD24hi/CD27+B10 cells), CCR6+/CD123+/IDO+ DCs, and Tregs from ELTGF patients had similar or higher percentages versus HD (P<0.05). By contrast, number of Tregs, DCregs, and Bregs except for CD27+B10 cells from CGD patients had lower levels versus HD and ELTGF patients (P<0.05). The findings of this exploratory study might suggest that in ELTGF patients, peripheral tolerance mechanisms could be directly involved in the maintenance of a quiescent immunologic state and graft function stability.