Objective: To investigate the immune tolerance in liver transplantation in rats induced by dendritic cells (DCs) transfected with B and T lymphocyte attenuator (BTLA) gene mediated by lentivirus and the mechanism.
Methods: The animal models of orthotopic liver transplantation were established by using DA rats as donors and Lewis rats as recipient respectively. DCs were isolated from SD rats, and then were infected with recombinant lentivirus carrying or without BTLA gene, respectively. Thirty-six rats after liver transplantation were equally randomized into model group (without any treatment after liver transplantation), DC group (transfused with DCs without BTLA gene after liver transplantation) and BTLA-DC group (transfused with DCs bearing BTLA gene after liver transplantation). In each group of rats, after completion of serum biochemical tests and liver pathological examination on postoperative 7 d, the remaining rats were used for determining the survival time.
Results: After transplantation, the liver function injury parameters, immune-stimulating cytokine IFN-γ level and rejection pathological score of the liver transplant were decreased and the immune-inhibiting cytokine IL-10 was increased in BTLA-DC group, but all above variables presented an opposite trend in DC group compared with model group, and the differences in all quantitative variables had a statistical significance (all P<0.05). The mean survival times for model group, DC group and BTLA-DC group were 15, 13, and 79 d respectively, and difference in survival time had statistical significance among the three groups (χ2=16.14, P=0.000 3).
Conclusion: DCs with high BTLA expression can alleviate rejection reactions of the liver transplant and prolong the survival time of the recipient rats, and the mechanism may possibly be associated with its inducing T cell immune tolerance.