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

研究了供体免疫活性细胞在犬肝移植模型耐受诱导中的作用。我们特别分析了肝移植时供体骨髓细胞接种对受体的影响。实验以体重8 ~ 14kg的雌雄异种成年比格犬和杂种犬作为受体和供体。犬同种异体肝脏原位移植是我们的标准技术。将受体分为两组：第一组为对照组，无免疫抑制；II组，术后静脉滴注FK506 0.05mg/kg/d，持续14 d；第三组，在移植时进行供体骨髓接种的附加治疗；IV组，术后14天静脉滴注新研制的FK506脂质体制剂0.05mg/kg/d。从供体肋骨处获得供体骨髓细胞，静脉接种2X10^8细胞于受体体内。评估各组受者的生存天数。1组受者均在14天内死于严重急性排斥反应。II组5例受体中2例在2周内死亡，其余3例分别在第24、27、33天死于排斥反应。虽然III组的受者在移植后也存活了30-35天，但在本实验中没有发生诱导耐受。然而，在IV组中，尽管在第14天停止免疫抑制，5名受者中有3名存活超过200天。这些结果表明，重新研究利用供体骨髓诱导耐受的方法是必要的，脂质体FK506能够在肝移植中显示出吸引人的免疫抑制效果。

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.