Abstract
Accumulating evidence suggests that Th17 cells play a role in the development of chronic allograft injury in transplantation of various organs. However, the influence of current immunosuppressants on Th17-associated immune responses has not been fully investigated. We prospectively investigated the changes in Th17 cells in peripheral blood mononuclear cells (PBMCs) collected before and 1 and 3 months after KT in 26 patients and we investigated the suppressive effect of tacrolimus on Th17 in vitro. In the early posttransplant period, the percentage of Th17 cells and the proportion of IL-17-producing cells in the effector memory T cells (TEM) were significantly increased at 3 months after transplantation compared with before transplantation (P<0.05), whereas Th1/Th2 cells and TEM cells were significantly decreased. The degree of increase in Th17 during the early posttransplant period was significantly associated with allograft function at 1 year after transplantation (r = 0.4, P<0.05). In vitro, tacrolimus suppressed Th1 and Th2 cells in a concentration-dependent manner, but did not suppress Th17 cells even at high concentration. This suggests that current immunosuppression based on tacrolimus is inadequate to suppress Th17 cells in KTRs, and dysregulation of Th17 may be associated with the progression of CAD.
Highlights
After kidney transplantation, alloimmune responses by CD4+ T cell activation mediate most cases of allograft rejection [1]
During the early posttransplant period, in which most robust immune reactions develop, most effector T cell subsets are effectively suppressed by the current immunosuppressive protocol, which may result in the significant improvement in short-term clinical outcomes
Comparison of Th17 cell levels in patients with and without chronic allograft dysfunction (CAD). In another cohort, which was at least 5 years after transplantation, we evaluated the proportion of Th1, Th2 and Th17 cells in the CD4+ T cells and compared them in patients with and without CAD
Summary
Alloimmune responses by CD4+ T cell activation mediate most cases of allograft rejection [1]. Most immune suppressants have been developed to downregulate the activation and differentiation of effector CD4+ T cells to prevent the generation of these alloimmune responses [2,3]. The Tac-based immunosuppressive protocol has been shown to be more effective in preventing the development of acute rejection episodes and improving 1 year allograft survival than the previously used regimen based on azathioprine and steroids [4]. During the early posttransplant period, in which most robust immune reactions develop, most effector T cell subsets are effectively suppressed by the current immunosuppressive protocol, which may result in the significant improvement in short-term clinical outcomes. Long-term allograft survival has not improved significantly compared with that in the azathioprine era [5,6]
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