Background : Accumulating evidence suggests that Treg/Th17 axis have important role in long term allograft survival in kidney transplantation. The aim of this study is to compare the effect between tacrolimus (Tac) and sirolimus (SRL) in the regulation of Treg/Th17 axis.
Methods: To investigate the effect of SRL or Tac on Treg/Th17 axis, Th1 (IFN-g), Th2 (IL-4), Th17 (IL-17) and Treg (Foxp3+) were quantitatively determined upon T-cell-specific stimulation in blood mononuclear cells (PBMCs) from healthy individuals (n = 11; in vitro) and kidney-transplant patients (n = 5; ex vivo) under clinically relevant concentrations of SRL or Tac. In addition, we analyzed the changes in T cell subsets in peripheral blood mononuclear cells (PBMCs) using FACs analysis, mRNA levels using real-time PCR and signaling molecules using western blotting. In vivo, we investigated the change of T cell subset after conversion from Tac to SRL.
Results: In vitro, Tac suppressed Th1, Th2 and Treg cells in a concentration-dependent manner, but did not suppress Th17 cells even at high concentration. During therapy with SRL, without CNI, the Th1, Th2 and Th17 production was decreased, but the Treg was not decreased, in comparison to treatment with Tac. IL-17 mRNA levels were significantly decrease in treatment with SRL and CNI as compared with the Th17 condition. However, Foxp3 mRNA expression levels were significantly increased in treatment with SRL. Kidney Transplant recipients who took SRL showed decreased production of Th17 and Th2 cytokines in PBMC, compared to treatment with Tac.
Conclusion: This study suggests that SRL is superior in the regulation of Th17/Treg axis to Treg favorable condition compared to Tac., which may give benefit in long term allograft survival.
To cite this abstract in AMA style:Kim K, Chung B, Kim B, Cho M, Yang C. Differential Regulation of Regulatory T Cells and Th17 Cells by mTOR Inhibitor in Kidney Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/differential-regulation-of-regulatory-t-cells-and-th17-cells-by-mtor-inhibitor-in-kidney-transplant-recipients/. Accessed October 24, 2020.
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