The Study of the Immune Tolerance Induced by PD-L1Ig in Rat Liver Transplantation

［Abstract］Objective　To explore the effect of PD-L1Ig on the immune tolerance in rats with liver transplantation．Methods　Twenty ROLT models were established by Kamada two-cuff technique，with inbred male Wistar rats and male SD rats served as donor and recipient respectively．The recipients were randomly devided into 2 groups according to different treatments：no treatment A（Wistar→SD n＝10）and B treated with PD-L1Ig （Wistar→SD n＝10）after the day of operation， the following day，the fourth day and sixth day．The clinical characters，the animal survival，mental and appetite were observed．The liver and blood samples were taken form rats after one week for detecting liver function and proportions of CD4+CD25+Treg and observing the rejection of liver pathology．Results　In the treatment group，the liver function test，including serum alanine aminotransferase，aspartate aminotransferase and total bilirubin，was superior to control group（P < 0.05）．Pathology of liver revealed there were a large number of mononuclear cells around the portal tract area in blank control group. The inflammation of PD-L1Ig group was relatively less serious，only a little accumulation of inflammatory cells．The liver rejection of blank control was more serious than PD-L1Ig group．Referencing Baff marking，the rejection was moderate and severe in group of PD-L1Ig and blank control，respectively．The group of PD-L1Ig showed a lower immune response and lighter rejection of liver than the control group. Flow cytometry analysis of CD4+ CD25+ Treg showed that the proportion of peripheral blood CD4+CD25+Treg cells in PD-L1Ig group was significantly higher than control group（P＜0.05）．Therefore，PD-L1Ig group rats showed better negative regulator activity of immune cell． Conclusions　The liver functions of PD-L1Ig treated rats are better．A low immune response can be induced in the rats of ROLT by PD-L1Ig treatment．The proportion of peripheral blood CD4+CD25+Treg increases after liver transplantation in rats，which might be a mechanism of immune tolerance.