Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation / 器官移植

ABSTRACT

Objective To investigate the relationship between immune tolerance and the changes of helper T cell (Th), regulatory T cell (Treg) cytokines, related signaling pathway proteins during immune tolerance process in rat models of liver transplantation. Methods The orthotopic liver transplantation rat models were established by double-cuff technique. All rats were divided into 3 groups. In the operative control group (n=6), sham operation was performed without liver transplantation. In the short-term group (n=10), the rats survived for 10 d after liver transplantation. In the immune tolerance group (n=10), the rats survived for 100 d after operation and the function of the transplanted liver was restored to normal. The expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Th1 cytokines [interferon (IFN)-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α], Th2 cytokines (IL-4, IL-5, IL-6 and IL-13), Th17 cytokines [granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A], Treg cytokines [IL-10, transforming growth factor (TGF)-β and IL-12p] were quantitatively measured. The serum sample of rats in each group was detected by protein chip analysis. Results Compared with the operative control group, the AST level in the short-term group was significantly down-regulated, whereas the ALT level was significantly up-regulated (both P < 0.05). However, the AST and ALT levels did not significantly differ between the immune tolerance group and operative control group (both P > 0.05). In the liver tissues of rats in each group, the expression levels of Th1 cytokines IFN-γ and IL-2 in the short-term group were significantly higher than those in the operative control group (both P < 0.05). The expression level of Th2 cytokine IL-4 in the immune tolerance group was significantly lower than that in the operative control group (P < 0.05). The expression levels of Th2 cytokines IL-5, IL-6 and IL-13 in the short-term group were significantly lower than those in the operative control group (all P < 0.05). The expression level of IL-17A in the immune tolerance group was significantly higher than that in the operative control group (P < 0.05). In the immune tolerance group, the expression levels of IL-10and IL-12p were significantly higher than those in the operative control group (both P < 0.05). The expression level of TGF-β in the short-term group was significantly higher than that in the operative control group (P < 0.05). Compared with the operative control group, the expression levels of intercellular adhesion molecule (ICAM)-1, pro-platelet basic protein (Ppbp), Neuropilin-2, Notch-2 protein in the short-term group were significantly up-regulated (all P < 0.05). The expression levels of CXC chemokine ligand 17 (CXCL17), ICAM-1 and Neuroleptin-2 protein were markedly up-regulated (all P < 0.05), whereas that of B7-1 protein was significantly down-regulated (P < 0.05) in the immune tolerance group. Conclusions Treg cytokines (IL-10, TGF-β and IL-12p), IL-6, IL-17 and trans-membrane signaling pathway molecules (ICAM-1, Neuropilin-2, B7-1 proteins) play a pivotal role in the natural immune tolerance process of rat models of liver transplantation.