The roles of T helper type 17/regulatory T cells in acute rejection after liver transplantation in rats.

Background: Liver transplantation is a widely accepted treatment for end-stage liver disease. The aim of our study was to investigate the imbalance between T helper type 17 (Th17) and CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells during hepatic allograft rejection in a rodent grafts model because their roles in liver transplantation is not fully understood.

Methods: We compared median survival time (MST) survivals, Th17/Treg cells and related cytokines levels (interleukin [IL]-17, IL-6, IL-10, and transforming growth factor-β1), as well as serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T-Bili) after liver transplantation. In addition, the allograft groups were injected with IL-17 neutralizing antibody to evaluate the role of IL-17 in acute rejection.

Results: Th17 cells and related cytokines (IL-17 and IL-6) were obviously increased in the allograft group (all P < 0.01), whereas Treg cells and related cytokines (IL-10 and transforming growth factor-β1) were markedly lower than those of isograft and control groups (all P < 0.01). In addition, liver grafts in allograft groups rejected acutely (MST, 8.0 ± 1.2 days) accompanied by impaired liver function (AST, ALT, and T-Bili), while isograft groups survived long term (MST, 50.0 ± 3.8 days, all P < 0.01 vs. allograft group). Finally, neutralization of IL-17 in allograft groups significantly prolonged the survival (MST, 32.0 ± 4.8 days, P < 0.01), improved the liver function (AST, ALT, and T-Bili), and increased Treg cells in the liver (all P < 0.01).

Conclusions: Th17 cells and secreted IL-17 play critical roles in acute rejection after liver grafts. The reduction of IL-17 may be 1 mechanism of immune tolerance after liver transplantation.