Preoperative application of combination of portal venous injection of donor spleen cells and intraperitoneal injection of rapamycin prolongs the survival of cardiac allografts in mice

Objective:To investigate the effects of preoperative portal venous injection of donor spleen cells(PVIDSC) and intraperitoneal injection of rapamycin in the acute rejection of cardiac allograft in mice and the underlying mechanisms. Methods:Homogenous female B6 mice and BALB/c mice were used as recipients and donors of heart transplantation. These mice were randomly divided into different groups and received PVIDSC alone,rapamycin alone,or PVIDSC and rapamycin combined therapy. In addition,the underlying mechanism was studied by measuring a number of cytokines. Results:Preoperative combination of PVIDSC and intraperitoneal injection of rapamycin significantly prolonged the survival of heterotopic cardiac allograft in mice,but had no effects on the survival time of cardiac allografts in mice pre-sensitized by skin grafting. Preoperative combination of PVIDSC and intraperitoneal injection of rapamycin increased the expression of IL-10 and Foxp3 and reduced the expression of INF-γ. Short-term preoperative administration of rapamycin promotes the expression of CD4+CD25+Foxp3+regulator T cells. However,preoperative using alone of rapamycin,or combination of PVIDSC and rapamycin had no effects on the inhibition of proliferation of memory T cells. Conclusions:Preoperative application of combination of PVIDSC and rapamycin significantly prolonged the survival time of cardiac allografts in mice but not in mice pre-sensitized by skin grafting. This may be explained by the fact that combination of PVIDSC and rapamycin inhibited the cellular immune response and induced the expression of IL-10 from Tr1 cells and CD4+CD25+FoxP3+regulatory T cells.