DEVELOPMENT OF CLINICALLY APPLICABLE STRATEGIES TO INDUCE AND MONITOR LONG TERM ACCEPTANCE OF LIVER ALLOGRAFTS

肝移植是终末期肝病的唯一疗法，这种治疗挽救了成千上万澳大利亚人的生命。肝移植的主要并发症是排斥反应，这导致大约一半的移植肝脏在十年内丢失。在许多动物模型中，肝移植不会被排斥，并且在动物的一生中功能正常。使用这样的一个动物模型，我们已经表明，来自供体的白色细胞是没有排斥反应的原因。有趣的是，这些细胞似乎刺激了快速和极端的免疫反应，这与排斥反应非常相似。主要的区别是，它比拒绝更快，更明显，然后耗尽自己。这一观察结果是出乎意料的，并提出了新治疗的可能性。此外，它质疑我们目前治疗肝移植排斥反应的有效性。我们已经证明，某些用于预防人类排斥反应的药物实际上在动物模型中产生了相反的效果，并阻止了肝脏移植的长期接受。这项工作的目的是在我们的动物模型中开发一种更好的治疗人类肝移植患者的方法。这将包括注射供体白色细胞和用促进这些细胞的有益作用的药物治疗。我们还将开发在移植后早期检测人类肝移植患者的血液或肝脏的方法，以确定患者是否接受肝脏。这意味着一旦在动物模型中优化，我们应该能够在肝移植患者中尝试这种新的治疗方法。

Liver transplantation is the only therapy for end-stage liver disease and thousands of Australian lives have been saved with this treatment. The major complication of liver transplantation is rejection which leads to loss of about half of the transplanted livers by ten years. Liver transplants in many animal models are not rejected and function normally for the life of the animal. Using one such animal model we have shown that white cells from the donor are responsible for the absence of rejection. Of interest, these cells appear to stimulate a rapid and extreme immune response, which closely resembles rejection. The main difference is that it is quicker and more marked than rejection and then exhausts itself. This observation is unexpected and suggests possibilities for new treatments. Furthermore it questions the effectiveness of our present treatment for rejection of transplanted livers. We have already shown that some kinds of drugs given to prevent rejection in humans actually have the opposite effect in the animal model and prevent long-term acceptance of liver transplants. The aim of this work is to develop in our animal model a better way of treating human liver transplant patients. This will incorporate injection of donor white cells and treatment with drugs which promote the beneficial effects of these cells. We will also develop ways of testing the blood or the liver of the human liver transplant patients early after transplantation to find out whether the patient is accepting the liver or not. This means that we should be able to try this new treatment method in liver transplant patients once it has been optimised in the animal model.