| Objective: To investigate the influence of pre-infusion of spleen cells from dexamethasone-treated rats in vivo on allograft survival of liver cirrhosis rats orthotopic liver transplantation, and develop new ideas and feasible ways for induction of clinic transplantation immune tolerance under no common immunosuppression.Methods: The animal model of liver cirrhosis was made with carbon tetrachloride, and the two-cuff orthotopic liver transplantation was performed. Wistar rats were used as donors, and SD rats as recipients. The SD rats were divided into normal liver function group, normal operation control group(N-Control), liver cirrhosis operation control group(C-Control), dexamethasone group(Dex), spleen cells group(SpC) and dexamethasone-treated spleen cells group(Dex-SpC). The N-Control and C-Control have nothing treatment; The Dex donor rats were treated with dexamethasone but the recipient rats did not infuse spleen cells; The SpC recipient rats were infused intravenously with donor spleen cells(5×107) 7 days before transplantation but the donor rats were not treated with dexamethasone; The Dex-SpC recipient rats were infused intravenously with dexamethasone-treated donor spleen cells(5×107) 7 days before liver transplantation. The survival time of each groups were observed. The blood alanine transaminase(ALT), total bilirubin(TBil) and liver pathological changes of each groups were observed 1 week after the transplantation. Apoptotic percentage of spleen cells from dexamethasone-treated rats in vivo was measured by flow cytometry using Annexin V/PI double staining method.Results: (1) The median survival time(MST) of N-Control, C-Control and Dex was 9, 18 and 15 days respectively, and had no difference each other(P>0.05). The MST of group infused donor spleen cells was 34 days, and had significant difference to other groups (P<0.01). The MST of group infused with donor in vivo dexamethasone-treated spleen cells was no lessthan 100 days, showed long-term survival, and had significant difference to other groups(P<0.01). (2) ALT, TBil in C-Control, N-Control and Dex group were increased significantly 7 days after operation. ALT, TBil were better in non-treated donor spleen cells group and the best in dexamethasone-treated donor spleen cells. (3) Rejection active index(RAI) of liver acute rejection pathology in C-Control, N-Control and Dex were between 6 and 9, and have no difference each other(P>0.05). RAI in non-treated donor spleen cells group were between 4 and 6 and had significant difference to other groups (P<0.01). RAI in dexamethasone-treated donor spleen cells were between 3 and 5 and had significant difference to other groups (P<0.01). (4) Dexamethasone-treated in vivo administrated induced donor spleen cells apoptosis (32.40±5.61% ) , while the non-treated groups did not(0.77± 0.11%).Conclusions: Immune tolerance can be induced by infusion of preoperative donor dexamethasone-treated spleen cells in liver cirrhosis rats liver allograft. Dexamethasone induces donor rats spleen cells apoptosis in vivo. Infusion of the apoptotic spleen cells provides not only the apoptotic cells, but also the donor antigen. Phagocytosis of these apoptotic spleen cells by phagocytes of recipient provides an immunosuppressive circumstance. Under this immunosuppressive circumstance, the recipient lymphocytes do not react to the donor antigen presented by antigen presenting cells, and do not react to the engrafted allograft subsequently. |
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