Koyama I, Williams M, Cameron J L, Zuidema G D
Transplantation. 1986 Oct;42(4):333-6. doi: 10.1097/00007890-198610000-00001.
Experiments were carried out in outbred dogs and pigs to evaluate the relative immunogenicity of pancreatic islets and segmental pancreas grafts, and whether these could be ameliorated by transplanting a kidney simultaneously from the same donor animal. Various immunosuppressive regimens were also studied. Pancreatic islet allografts never normalized blood glucose in totally pancreatectomized recipients despite the use of cyclosporine (CsA) in high doses (40 mg/kg/day) and the simultaneous transplantation of a kidney from the same donor. These grafts which never "took" contrast sharply with the experience of pancreatic islet autografts prepared in the same way and inoculated into the spleen, which in all nine instances normalized blood glucose in pancreatectomized recipients. Segmental transplants were performed in swine with duct drainage into the jejunum. Totally pancreatectomized pigs died at 7.8 +/- 1.0 days. In recipients suppressed with low-dose azathioprine (Az) and prednisone (Pred) pancreas grafts alone were rejected in 12.9 +/- 10 days. Synchronous pancreas and kidney transplants treated similarly extended the mean survival of pancreatic grafts to 20 +/- 10 days--which, however, was not significant (P less than 0.1 greater than 0.05). Mean survival time of pancreatic grafts in recipients receiving CsA at 20 mg/kg/day and prednisone 1 mg/kg/day was 14 +/- 6.3 days. The combination of CsA 20 mg/kg/day, Az 2 mg/kg/day, and Pred 1 mg/kg/day prolonged the mean survival time to 39.8 +/- 22 days. These results allow us to conclude that: crude preparations of islet tissue invariably capable of normalizing blood sugar at day 4 when used as autografts failed to "take" despite the existence of alternative sources of antigen present in a well vascularized kidney from the same donor, and despite very high dosages of CsA; triple immunosuppressive therapy had synergistic effects on pancreatic allograft survival; and simultaneous transplantation of kidney and pancreas had little effect on survival times of the pancreas or the kidney.
在远交系犬和猪身上进行了实验，以评估胰岛和节段性胰腺移植物的相对免疫原性，以及同时移植来自同一供体动物的肾脏是否可以改善这种情况。还研究了各种免疫抑制方案。尽管使用了高剂量（40mg/kg/天）的环孢素（CsA）并同时移植来自同一供体的肾脏，但胰岛同种异体移植物在全胰切除受体中从未使血糖正常化。这些从未“存活”的移植物与以相同方式制备并接种到脾脏中的胰岛自体移植物的情况形成鲜明对比，在所有9例中，胰岛自体移植物均使全胰切除受体的血糖正常化。在猪身上进行了节段性移植，将导管引流至空肠。全胰切除的猪在7.8±1.0天死亡。在接受低剂量硫唑嘌呤（Az）和泼尼松（Pred）抑制的受体中，仅胰腺移植物在12.9±10天被排斥。同样处理的同期胰腺和肾脏移植将胰腺移植物的平均存活时间延长至20±10天——然而，这并不显著（P小于0.1大于0.05）。接受20mg/kg/天CsA和1mg/kg/天泼尼松的受体中胰腺移植物的平均存活时间为14±6.3天。20mg/kg/天CsA、2mg/kg/天Az和1mg/kg/天Pred的联合使用将平均存活时间延长至39.8±22天。这些结果使我们能够得出以下结论：胰岛组织粗制品作为自体移植物使用时在第4天总是能够使血糖正常化，但尽管存在来自同一供体的血管丰富的肾脏中的替代抗原源，并且尽管使用了非常高剂量的CsA，却未能“存活”；三联免疫抑制疗法对胰腺同种异体移植物存活有协同作用；同时移植肾脏和胰腺对胰腺或肾脏的存活时间几乎没有影响。
