MECHANISM OF TRANSPLANT CHIMERISM AND SIGNIFICANCE OF MIGRATION OF DONOR-DERIVED CELLS IN ORGAN

本研究探讨供体免疫活性细胞在犬肝移植免疫耐受诱导中的作用。本实验选用体重8- 14 kg的成年Beagle犬和杂种犬作为受体和供体，研究了供体骨髓细胞在肝移植时对受体的影响。犬同种异体原位肝移植是我们的标准技术。实验分为三组：Ⅰ组，对照组，不使用免疫抑制剂，Ⅱ组，术后静脉注射FK 506 0.05mg/kg/d，共14天，Ⅲ组，Ⅱ组在移植时加用供者骨髓接种，Ⅳ组，IV组术后静脉注射新研制的FK 506脂质体制剂0.05mg/kg/d，连续14天。从供体肋骨获得供体骨髓细胞，并将2 × 10^8个细胞静脉接种到受体中。观察各组受者存活时间，I组受者均在14天内死于严重急性排斥反应。Ⅱ组5只受体中有2只在2周内死亡，3只分别于第24、27、33天死于排斥反应。虽然第III组的受体也存活至移植后30-35天，但在本实验中未发生耐受诱导。IV组5例中有3例在第14天停止免疫抑制后仍存活超过200天。提示：对供体骨髓诱导耐受的方法进行重新研究是必要的，FK 506脂质体在肝移植中具有良好的免疫抑制效果。

We investigated the role of donor immunocompetent cells on the tolerance induction of canine liver transplantation model. Especially, we analyzed the effect of donor bone marrow cells inoculation to the recipient at the time of liver transplantation.Outbred young adult beagle and mongrel dogs of both sexes, weighing 8-14kg were used as recipient and donor in experiment. Orthotopic canine allotransplantation of the liver was performed as our standard technique. The recipients were divided into the following groups : Group I,controls, no immunosuppression ; Group II,0.05mg/kg/day FK506 administered intravenously for 14 days postoperatively ; Group III,additional treatment of donor bone marrow inoculation at the time of transplantation in group II ; Group IV,0.05mg/kg/day of FK506 administered intravenously newly developed liposomal formulation for 14 days postoperatively. Donor bone marrow cells were obtained from donor ribs and inoculated 2X10^8 cells in recipients intravenously. The recipient survival days were evaluated in each groups.All recipients in group I died of severe acute rejection within 14 days. In group II,two of five recipients died within 2 weeks and remaining 3 recipients died of rejection on days 24,27,33, respectively. Although, recipients in group III also survived until 30-35 days after transplantation, induction of tolerance was not occurred in this experiment. However, in group IV,three of five recipients survived for more than 200 days despite discontinuation of immunosuppression on day 14.These results suggested that re-investigation of method for torelance induction by using donor bone marrow is essential and liposomal FK506 is able to reveal attractive immunosuppressive efficacy in liver transplantation.