Application Of CTLA4-Ig In The Prevention Of Rejection And The Induction Of Immune Tolerance Of Orthotopic Liver Transplantation In Rats

Objective This study was conducted to build experimental model of ROLT (orthotopic liver transplantation in rat) with the character of acute rejection; and, to study the effect of CTLA4-Ig on preventing in ROLT. Methods First, study the skills for building model of ROLT in wistar rats performed by the two cuff method. And then, rats were randomly divided into two groups; Group wistar→SD ROLT group; and group SD→wistar ROLT. Select the group whose character of acute rejection was stable. And last, build the model with rejection for following studies. Recipients were randomly divided into the following groups according to different treatments: no treatment A (wistar→wistar, n=13); no treatment B (wistar→SD, n=13); and C treated with CTLA4-Ig (wistar→SD, n=13) after 2 days of operation. The clinical characters, the liver function, the transplantated liver pathologic character and the concentrations of IL4, IL10, TNF- α in serum was observed and measured on postoperative day 7. In group A and C, all above observation were done on postoperative month 4. Above all, determine the effect of CTLA4-Ig on preventing acute rejection and inducing tolerance in ROLT. Results (1) Recipients (no treatment B) died one by one within 6th~14thdays, and SD—>wistar recipients lived little longer than wistar-*SD, but wistar—>wistar recipients could lived for long time without any rejection. (2) In treatment group, on postoperative day 7, no clinical rejection respond character, no pathologic character of rejection in transplantation liver, and no serum concentration of cytokins related to IL-4, IL-10, TNF-a increasing found. (3) In treatment group, recipients could live for long time healthily, no abnormal pathologic liver characters, no abnormal serum concentration of cytokins.Conclusion (1) wistar-*SD ROLT model possessed stable characters of acute rejection (2) CTLA4-Ig treatment alone inhibits rejection responds in ROLT. (3) CTLA4-Ig treatment can induce tolerance in ROLT model with characters of acute rejection. (4) The serum concentration of cytokins related to IL4, IL10,TNF-a can be used as evaluation standard of rejection in ROLT rejection.