Application of Cytotoxic T Lymphocyte Antigen 4 Immunoglobulin G in Prevention of Rejection and the Induction of Immune Tolerance of Orthotopic Liver Transplantation in Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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Cytotoxic T lymphocyte antigen 4 immunoglobulin G Liver transplantation Rat RejectionImmune tolerance

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【Abstract】Objective This study was conducted to build experimental model of orthotopic liver transplantation in rat (ROLT) with the character of acute rejection; and to study the effect of cytotoxic T lymphocyte antigen 4 immunoglobulin G (CTLA4Ig) on prevention of rejection and the induction of immune tolerance of ROLT. Methods Build model of Wistar→SD ROLT(performed by the two cuff method) with character of acute rejection.Recipients were injected with CTLA4Ig 75 μg per ROLT into abdominal cavity after 2 days of operation. Contrast was made with no treatment group, the clinical characters, the liver function, the transplantated liver pathologic character and the concentrations of TNFα in serum were observed and measured on postoperative day 7. In treatment group, all above observation were done on postoperative month 4. Above all, determination of the effect of CTLA4Ig on preventing acute rejection and inducing tolerance in ROLT was observed.Results ①Recipients (no treatment group) died one by one within 6th～14th days; pathologic character of rejection in transplantation liver could be found; ② In treatment group, on postoperative day 7 and month 4, no clinical rejection character and no pathologic character of rejection in transplantation liver were found and serum concentration of cytokins related to TNFα found lower than that of contrast group(P＜0.05), and serum concentration of ALT、AST、TBIL、DBIL found lower too(P＜0.05); But serum concentration of TP and Alb was found higher than that of contrast group(P＜0.05).

Conclusion ① CTLA4Ig treatment alone inhibits the rejection responce in ROLT. ② CTLA4Ig treatment can Prevent rejection and induce immune tolerance in ROLT model with characters of acute rejection; the serum concentration of cytokins related to TNFα can probably be used as evaluation standard of rejection in ROLT rejection.

Citation： ZHI Xing,YAN Lnan YANG Pei,XIANG Chunhua.. Application of Cytotoxic T Lymphocyte Antigen 4 Immunoglobulin G in Prevention of Rejection and the Induction of Immune Tolerance of Orthotopic Liver Transplantation in Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2005, 12(6): 600-604. doi: Copy

1 Renna Molajoni E, Cinti P, Orlandini AM, et al. Contribution of the direct and indirect allorecognition pathway to the rejection of liver allografts [Ｊ]. Transplant Proc, 1998; 30(5)21382 RennaMolajoni E, Cinti P, Evangelista B, et al. Role of the indirect recognition pathway in the development of chronic liver allograft rejection [Ｊ]. Transplant Proc, 1998; 30(5)21403 Vierling JM. Immunology of acute and chronic hepatic allograft rejection [Ｊ]. Liver Transpl Surg, 1999; 5(4 Suppl 1)S14 Bretscher P. The twosignal model of lymphocyte activation twentyone years later [Ｊ]. Immunol Today, 1992; 13(2)745 Lafferty KJ. A few steps along the path to adult transplantation tolerance [Ｊ]. Transplant Proc, 1999; 31(1-2A)11S6 No authors listed. Banff schema for grading liver allograft rejection: an international consensus document [Ｊ]. Hepatology, 1997; 25(3)6587 Neumann UP, Fischer U, Schmitz V, et al. Longterm graft acceptance after rat liver allograft transplantation induced by application of CTLA4Ig and donor specific spleen cell administration [Ｊ]. Transplant Proc, 2002; 34(5)14008 Li W, Lu L, Wang Z, et al. CTLA4Ig inhibits rejection of mouse liver allografts from Flt3ligandtreated donors and is associated with increased lymphocyte apoptosis [Ｊ]. Transplant Proc, 2001; 33(1-2)2469 Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Longterm survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig [Ｊ]. Science, 1992; 257(5071)78910 Larsen CP, Elwood ET, Alexander DZ, et al. Longterm acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways [Ｊ]. Nature, 1996; 381(6581)43411 Kirk AD, Harlan DM, Armstrong NN, et al. CTLA4Ig and antiCD40 ligand prevent renal allograft rejection in primates [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(16)878912 陈实. 器官移植研究的热点与争议问题 [A]. 见陈实主编. 移植学前沿 [M]. 武汉：湖北科学技术出版社， 20026~713 Platz KP, Mueller AR, Rossaint R, et al. Cytokine pattern during rejection and infection after liver transplantation——mprovements in postoperative monitoring? [Ｊ]. Transplantation, 19967; 62(10)144114 Moudgil A, Bagga A, Toyoda M, et al. Expression of gammaIFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients [Ｊ]. Clin Transplant, 1999; 13(2)20115 Paul LC. Surrogate biomarkers of longterm outcome after kidney transplantation [Ｊ]. Ann Transplant, 2000; 5(2)516 陈忠华. 移植免疫耐受 [A]. 见陈实主编. 移植免疫学 [M]. 武汉：湖北科学技术出版社， 1998298~31217 Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins [Ｊ]. Science, 1954; 102(2)400.

1. 1 Renna Molajoni E, Cinti P, Orlandini AM, et al. Contribution of the direct and indirect allorecognition pathway to the rejection of liver allografts [Ｊ]. Transplant Proc, 1998; 30(5)21382 RennaMolajoni E, Cinti P, Evangelista B, et al. Role of the indirect recognition pathway in the development of chronic liver allograft rejection [Ｊ]. Transplant Proc, 1998; 30(5)21403 Vierling JM. Immunology of acute and chronic hepatic allograft rejection [Ｊ]. Liver Transpl Surg, 1999; 5(4 Suppl 1)S14 Bretscher P. The twosignal model of lymphocyte activation twentyone years later [Ｊ]. Immunol Today, 1992; 13(2)745 Lafferty KJ. A few steps along the path to adult transplantation tolerance [Ｊ]. Transplant Proc, 1999; 31(1-2A)11S6 No authors listed. Banff schema for grading liver allograft rejection: an international consensus document [Ｊ]. Hepatology, 1997; 25(3)6587 Neumann UP, Fischer U, Schmitz V, et al. Longterm graft acceptance after rat liver allograft transplantation induced by application of CTLA4Ig and donor specific spleen cell administration [Ｊ]. Transplant Proc, 2002; 34(5)14008 Li W, Lu L, Wang Z, et al. CTLA4Ig inhibits rejection of mouse liver allografts from Flt3ligandtreated donors and is associated with increased lymphocyte apoptosis [Ｊ]. Transplant Proc, 2001; 33(1-2)2469 Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Longterm survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig [Ｊ]. Science, 1992; 257(5071)78910 Larsen CP, Elwood ET, Alexander DZ, et al. Longterm acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways [Ｊ]. Nature, 1996; 381(6581)43411 Kirk AD, Harlan DM, Armstrong NN, et al. CTLA4Ig and antiCD40 ligand prevent renal allograft rejection in primates [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(16)878912 陈实. 器官移植研究的热点与争议问题 [A]. 见陈实主编. 移植学前沿 [M]. 武汉：湖北科学技术出版社， 20026~713 Platz KP, Mueller AR, Rossaint R, et al. Cytokine pattern during rejection and infection after liver transplantation——mprovements in postoperative monitoring? [Ｊ]. Transplantation, 19967; 62(10)144114 Moudgil A, Bagga A, Toyoda M, et al. Expression of gammaIFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients [Ｊ]. Clin Transplant, 1999; 13(2)20115 Paul LC. Surrogate biomarkers of longterm outcome after kidney transplantation [Ｊ]. Ann Transplant, 2000; 5(2)516 陈忠华. 移植免疫耐受 [A]. 见陈实主编. 移植免疫学 [M]. 武汉：湖北科学技术出版社， 1998298~31217 Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins [Ｊ]. Science, 1954; 102(2)400.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Application of Cytotoxic T Lymphocyte Antigen 4 Immunoglobulin G in Prevention of Rejection and the Induction of Immune Tolerance of Orthotopic Liver Transplantation in Rats

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