Wennberg L, Karlsson-Parra A, Sundberg B, Rafael E, Liu J, Zhu S, Groth C G, Korsgren O
Department of Transplantation Surgery, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Transplantation. 1997 May 15;63(9):1234-42. doi: 10.1097/00007890-199705150-00008.
Morphological characteristics of islet xenograft rejection differ from those of islet allograft rejection. Therefore, prevention of islet xenograft rejection probably requires a different type of immunosuppression from that used in allogeneic transplantation.
Fetal porcine islet-like cell clusters (ICC) were transplanted into the renal subcapsular space of rats treated with different immunosuppressive protocols. The existence of a cellular infiltrate or deposits of antibodies and complement in the grafts was evaluated at different times after transplantation using immunohistochemistry.
Treatment with leflunomide (LEF), cyclosporine (CsA), mycophenolate mofetil (MMF), 15-deoxyspergualin, and rapamycin alone or in combination had an insufficient inhibitory effect on ICC xenograft rejection. However, in animals treated with LEF+CsA, the rejection process was markedly inhibited. However, some macrophages and T cells were still present, and at 24 days, the xenografts were destroyed. In LEF+CsA-treated animals that were given sera containing an excessive amount of rat anti-porcine xenoreactive antibodies, marked deposits of IgG, and to some extent C3 as well, were detected along the border between intact ICC, and the xenografts were surrounded by macrophages. However, almost no cells infiltrated the grafts, and there were many intact ICC. In animals treated with LEF+CsA+MMF, only occasional infiltrating cells were seen at 12 and 24 days after transplantation, and the endocrine tissue was completely intact.
LEF+CsA+MMF prevented rejection of porcine ICC xenografts in the rat for up to 24 days after transplantation.
胰岛异种移植排斥的形态学特征与胰岛同种移植排斥不同。因此，预防胰岛异种移植排斥可能需要不同于同种异体移植中使用的免疫抑制类型。
将胎猪胰岛样细胞团（ICC）移植到接受不同免疫抑制方案治疗的大鼠肾被膜下间隙。移植后不同时间使用免疫组织化学评估移植物中细胞浸润或抗体及补体沉积的存在情况。
单独或联合使用来氟米特（LEF）、环孢素（CsA）、霉酚酸酯（MMF）、15 - 去氧精胍菌素和雷帕霉素对ICC异种移植排斥的抑制作用不足。然而，在接受LEF + CsA治疗的动物中，排斥过程受到明显抑制。不过，仍有一些巨噬细胞和T细胞存在，并且在24天时，异种移植物被破坏。在接受LEF + CsA治疗且给予含有过量大鼠抗猪异种反应性抗体血清的动物中，在完整ICC的边界处检测到明显的IgG沉积，以及在一定程度上的C3沉积，并且异种移植物被巨噬细胞包围。然而，几乎没有细胞浸润移植物，并且有许多完整的ICC。在接受LEF + CsA + MMF治疗的动物中，移植后12天和24天时仅偶尔可见浸润细胞，并且内分泌组织完全完整。
LEF + CsA + MMF在移植后长达24天内预防了大鼠猪ICC异种移植物的排斥。
