Early biological and immune response to semi-identical liver or kidney allograft in miniature swine.

ABSTRACT

In inbred miniature swine, semi-identical liver allograft recipients survive up to 3 months without immunosuppression, whereas similarly mismatched kidney allografts are uniformly rejected within 2 weeks. The early biological and immunological events were assessed in this unique model. SLA(d/d) pigs (MGH, Harvard Medical School, Boston, MA, USA) received liver or kidney allograft from heterozygous SLA(c/d) miniature swine. Survival, graft function, histology, intragraft cytokines, peripheral lymphocyte and platelet count, plasma cortisol level and cellular/humoral anti-donor immune response were assessed. Kidney allografts were uniformly rejected within 2 weeks, whereas liver allografts survived for up to 87 days. After both liver and kidney transplantation, the peripheral lymphocyte count decreased during the first week concomitantly to a significant elevation of plasma cortisol level. Early decrease of peripheral platelet count was observed after liver but not renal transplantation. Up-regulation of transforming growth factor beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) was observed during the first postoperative week in semi-identical liver allografts and IFN-gamma as well as IL-10 in kidney allografts. In liver recipients, labelled autologous lymphocytes accumulated in the liver graft and native spleen, whereas after renal allograft, lymphocytes accumulated in the native spleen and liver but never in the kidney allograft. Specific cellular anti-donor unresponsiveness was observed from the first post-transplant day in both liver and kidney recipients, while the humoral anti-donor response remained intact. In semi-identical liver allograft, recipient rejection is milder and slower than in similarly matched kidney allograft. The intragraft up-regulation of TGF-beta1 in semi-identical liver allograft might be one mediator to explain the modulation of rejection after liver transplant. The rapid, nonspecific accumulation of recipient lymphocytes in the liver allograft but not in kidney allograft might also play a role in the different survival time in this model.