Experimental Study On Immune Tolerance Induced By A Short Course Of Lower Doses Of FK₅₀₆ In Hepatic Cirrhosis Rats After Liver Transplantation

Objective: To explore the feasibility and possible mechanisms of the immune tolerance induced by a short course of lower doses of FK₅₀₆ after liver transplantation.it provide the theoretical basis for the reasonal administration of immunosuppreant. Methods: The model was established by two-cuff technique orthotopic liver Transplantation (OLT) from Lews to cirrhosis BN rats.according to the dosage and timing of FK₅₀₆ after OLT, recipients were randomed into 5 groups: control, treated (1-4d) with lower-, middle-, larger- and delayed (4-7d) lower-dosage of FK₅₀₆. the post-OLT survival time were recorded and pathological changes of grafts were evaluated by Banff's standard. The IL-2, INF-γlevels, the Foxp3mRNA expression level and grafts Apoptosis were determined by ELISA, RT-PCR and TUNEL respectively on the 1^st-, 3^th-, 5^th- and 7^th-day after OLT. Results: Allografts rejection, apoptosis and the production of IL-2 and INF-γwere significantly suppressed by administration of larger-dosage of FK₅₀₆ in the early stage after OLT. Compared with the recipient rats with administration of larger-dosage of FK₅₀₆, the expression level of Foxp3mRNA of CD4⁺CD25⁺ regulatory T cells was higher and the mean survived time was longer in recipient rats with delayed lower doses of FK₅₀₆ after OLT. Conclusions: The mechanism of immunetolerance induced by a short course of delayed lower-dosage of FK₅₀₆ after OLT maybe correlated with the generation and activation of peripheral CD4+CD25+ regulatory T cells.