Adenovirus-mediated gene transfer of CD40Ig gene induced long-term survival of cardiac allograft in rats / 中国免疫学杂志

ABSTRACT

Objective:To induce long-term survival of cardiac allograft in rats by adenovirus-mediated gene transfer of CEMQIg gene, and to investigate the potential mechanisms involved in the induction of transplantation tolerance. Methods: The donor cardiac allograft from DA rats was heterotopically transplanted into the abdomen of LEW recipient rats, and recombinant adenoviruses containing EGFP gene or CD40Ig gene at a dose of 5 x ICf pfu were administered via portal vein, respectively, during the operation. The graft survival was monitored by daily palpation. The expression of CD4QIg fusion protein in the recipients was detected via EIISA. The tolerant mechanism was investigated via MLR, IL-2 reverse experiment and analyzing the expression of Thl/Th2 type cytokines in the recipients.Results: Compared with the untreated recipients, the mean survival time(MST) of the cardiac allograft was not prolonged in the recipients treated with AdEGFP adenovirus, whereas MST were prolonged significantly to 142.8 ?26.8 d in the recipients administered with AdCD40Ig adenovirus. The expression of CD40Ig fusion protein remained a long time but the levels gradually decreased. The results of MLR indicated that the induced tolerance in the recipients was donor-specific. The results of IL-2 reverse experiment demonstrated that the tolerance mechanisms were involved clonal anergy at the early stage of the established tolerance. The expression pattern of Thl/Th2 type cytokines did not indicate the polarization of Thl/Th2 type cytokines in the experimental models. Conclusion: A single injection of the defined dose of adenovirus containing CD40Ig gene via portal vein during operation is enough to induce long-term survival of cardiac allograft in rats.