丝裂霉素C预处理供体脾细胞和器官抑制小鼠心脏移植排斥反应

Pretreatment of donor splenocyte and graft with mitomycin C attenuates rejection in heart allograft transplantation in mice

目的观察丝裂霉素C（MMC）体外预处理供体脾细胞和器官的联合方案延长小鼠心脏移植物存活，探讨其作用机制。方法MMC体外处理供体脾细胞后输注给受体，并用MMC灌注供体心脏。结果经供体脾细胞输注联合器官预处理，小鼠移植物存活从7．0d延至28．5d。脾细胞输注或联合方案可使脾脏CIM＋CD25＋／CD4＋比例从15．0％降至7．4％、8．6％，CD4＋Foxp3＋／CIM＋比例从15．5％升至18．2％、18．6％。供体脾细胞经MMC处理后细胞凋亡从15．5％增至23．2％。结论静脉输注MMC处理的供体脾细胞或联合供体器官预处理，可明显延长小鼠心脏移植物存活。MMC可能通过供体细胞凋亡诱导调节性T细胞而发挥作用。

Objective To investigate the effect of pretreatment of donor splenocytes and grafts with mitomycin C （MMC） on heart allograft survival, and to demonstrate the mechanism of function. Methods Donor splenoeytes from donor mice were incubated with MMC in vitro and were then transfused into recipi- ent mice. The heart allograft was perfused with MMC prior to harvest. Results Donor splenocyte transfu- sion （DST） combined with MMC-graft pretreatment prolonged heart allograft survival fr.om 7. 0 to 28. 5 days. DST or combination strategy significantly decreased CIM ＋ CD25 ＋ population in CD4 ＋ T cells from 15.0% to 7. 4% and 8.6%, and meanwhile increased CIM＋ Foxp3＋ T cells from 15.5% to 18.2% and 18.6%. MMC incubation in vitro induced apoptosis of donor splenoeytes from 15.5% to 23.2%. Conclusion Transfusion of MMC-treated donor splenoeytes either alone or combined with graft pretreatment with MMC could significantly prolong heart allograft survival in mice. MMC pretreatment could induce apoptosis of donor cells, increase production of regulatory T cells, and thus achieve donor-specific immunosuppression.