Increased expression of non‐interleukin‐2 T cell growth factors and their implications during liver allograft rejection in rats

Abstract

Rejection remains a problem in the transplantation field. The aim of this study was to establish acute and chronic rejection models in rats and to investigate the roles of non-interleukin (IL)-2 T cell growth factors such as IL-15, IL-7 and IL-13 during rejection. A liver transplant model was established using Dark Agouti and Brown Norway rats. The rats were divided into group A, left without treatment; group B, received cyclosporinee (1 mg/kg/day); and group C, cyclosporinee (4 mg/kg/day). Histopathological, reverse transcriptase-polymerase chain reaction and western blot were performed in liver specimens obtained from different time-points after transplantation in the three groups. In group A, the livers showed irreversible acute cellular rejection with cell infiltration. In group B, chronic liver rejection was found, with graft infiltration, ductular damage or proliferation, obliterative arteriopathy and liver fibrosis. No apparent histological alterations were observed in group C. IL-15, IL-7 and IL-13 messenger RNA and their protein were all highly expressed in the liver specimens of groups A and B. Upregulated expression was found in IL-15 since the first day after transplantation and in IL-7 and IL-13 since day 6. The extent of IL-15 upregulation was more than that of IL-7 and IL-13. Liver transplantation in Dark Agouti to Brown Norway rats with low-dose immunosuppression can induce chronic rejection. In the process of acute and chronic allograft rejections, non-IL-2 T cell growth factors such as IL-15, IL-7 and IL-13 play roles. Strategies should pay more attention to regulating these cytokines after liver transplantation.