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 + /CD25 hi , 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 + /CD38 hi /CD24 hi /CD27 + B10 cells), CCR6 + /CD123 + /IDO + DCs, and Tregs from ELTGF patients had similar or higher percentages versus HD (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>). By contrast, number of Tregs, DCregs, and Bregs except for CD27 + B10 cells from CGD patients had lower levels versus HD and ELTGF patients (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>). 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.