Cederna J, Toledo-Pereyra L H, Gof S, Rios A, MacKenzie G H, Gordon D A
Immunol Commun. 1984;13(6):523-38. doi: 10.3109/08820138409061304.
Modification of graft immunogenicity using graft (GPTX) and donor pretreatment (DPTX) has been pursued in an attempt to modify allograft immunogenicity using various immunosuppressive agents. The murine skin allograft and canine renal allograft models were used to study the efficacy of Cyclosporine (Cy A) as a DPTX and GPTX prior to transplantation. Tail skin allografts from C3HHeN male mice were grafted to Balb/c female mouse recipients. Minimal immunosuppression was given to all skin graft recipients. Skin allograft were either GPTX with Cy A, DPTX with either Cy A, methylprednisolone (MP), or cyclophosphamide (CP), or Cy A GPTX and DPTX with the three drugs alone or in combination. Cy A GPTX alone of skin allografts did not significantly prolong survival. DPTX with Cy A significantly prolonged skin graft survival, however, CP or MP alone did not. The various combinations of MP, Cy A, and CP as DPTX and MP, Cy A, and CP DPTX used together with Cy A GPTX also significantly prolonged murine skin allograft survival. Kidney allografts used unrelated mongrel dogs as donors or recipients. Renal transplant experimental groups were either: Non-pretreated and immediately transplanted, nonpretreated and hypothermically stored (HS) for 24 hours in Collins (C-2) solution, GPTX with 12.5 mg Cy A during 24 hr. HS in C-2, DPTX with Cy A (25 mg/Kg), or Cy A DPTX (15 mg/kg) and GPTX during 24 hrs. HS in C-2. Cy A GPTX during HS was sometimes effective in prolonging kidney allograft survival greater than 30 days using only minimal immunosuppression with azathioprine. Cy A DPTX prolonged survival somewhat, but not significantly. Improved results were seen, however, when Cy A DPTX was used together with Cy A graft pretreatment. These results indicate the potential for the successful use of Cy A as a donor and/or graft pretreatment, however, further studies will be necessary to optimize the use of Cy A in these modalities.
人们一直在探索利用移植物预处理（GPTX）和供体预处理（DPTX）来改变移植物免疫原性，试图使用各种免疫抑制剂来改变同种异体移植物的免疫原性。小鼠皮肤同种异体移植和犬肾同种异体移植模型被用于研究环孢素（Cy A）作为移植前供体预处理和移植物预处理的效果。将C3HHeN雄性小鼠的尾部皮肤同种异体移植到Balb/c雌性小鼠受体上。所有皮肤移植受体都给予了最小限度的免疫抑制。皮肤同种异体移植要么用Cy A进行移植物预处理，要么用Cy A、甲基泼尼松龙（MP）或环磷酰胺（CP）进行供体预处理，或者用Cy A单独或与这三种药物联合进行移植物预处理和供体预处理。单独使用Cy A对皮肤同种异体移植进行移植物预处理并没有显著延长其存活时间。用Cy A进行供体预处理显著延长了皮肤移植的存活时间，然而，单独使用CP或MP则没有这种效果。MP、Cy A和CP作为供体预处理的各种组合，以及MP、Cy A和CP供体预处理与Cy A移植物预处理一起使用，也显著延长了小鼠皮肤同种异体移植的存活时间。肾同种异体移植使用无关的杂种犬作为供体或受体。肾移植实验组包括：未预处理并立即移植、未预处理并在柯林斯（C - 2）溶液中低温保存（HS）24小时、在24小时的C - 2溶液低温保存期间用12.5毫克Cy A进行移植物预处理、用Cy A（25毫克/千克）进行供体预处理，或在24小时的C - 2溶液低温保存期间用Cy A供体预处理（15毫克/千克）和移植物预处理。在低温保存期间用Cy A进行移植物预处理有时仅使用硫唑嘌呤进行最小限度的免疫抑制就能有效延长肾同种异体移植的存活时间超过30天。用Cy A进行供体预处理能使存活时间有所延长，但不显著。然而，当用Cy A进行供体预处理与Cy A移植物预处理一起使用时，效果有所改善。这些结果表明Cy A作为供体和/或移植物预处理成功应用的潜力，然而，还需要进一步研究以优化Cy A在这些方式中的使用。
