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.

Keywords: Belatacept; Cyclospirine; Kidney transplantation; Proinflammatory cells; Regulatory cells.