Immunophenotyping of peripheral immunoregulatory as well as Th17A and Th22 cell subpopulations in kidney transplant recipients under belatacept or cyclosporine treatment.

Abstract Objective Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induce peripheral tolerance, while Th17A and Th22 cell subpopulations are of proinflammatory nature. The aims of the study were to characterize and to enumerate peripheral Tregs, Bregs, and DCregs and Th17A and Th22 cell subpopulations in kidney transplant recipients (KTRs) under belatacept or cyclosporine treatment. Methods Forty-one KRT patients (30 under belatacept treatment and 11 under cyclosporine treatment) and 26 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 high Foxp3 + , and CD8 + /CD28 − Foxp3 + Tregs, CCR6 + /CD123 + /IDO + DCs, as well as Th17A and Th22 cell subpopulations were quantitated by flow cytometry. Results Of the IL-10-producing Bregs, CD19 + /CD24 high /CD38 high /CD5 + , CD19 + /CD24 high /CD38 high /CD10 + , CD19 + /CD24 high /CD38 high /CD20 + , and CD19 + /CD24 high /CD38 high /CD27 − had significant higher frequency in patients under belatacept treatment when compared with those under cyclosporine. Only CD19 + /CD24 high /CD38 high /CD27 + and CD19 + /CD24 high /CD38 high /CXCR7 + cells had significant higher frequency in patients under cycloporine treatment when compared to those under belatacept. The percentages of IDO-expressing pDC, CD4 + /CD25 high Foxp3 + , and CD8 + /CD28 − Foxp3 + were significantly higher in the belatacept group when compared the cyclosporine one, while Th17A and Th22 cells had significant higher frequency in the latter group. Conclusion Belatacept seems to maintain and enhance, at least systemically, a tolerant profile to renal allograft in transplant recipients by means of higher circulatory frequencies of regulatory B, T and pDC subpopulations.