Understanding rapid T-cell clearance by the liver: a critical step towards improved liver transplantation.

肝脏具有矛盾的特性：它是对病原体进行有效免疫反应的场所，但在某些情况下，它已知可以诱导无害的免疫反应。在移植环境中，不良反应可能是有益的，因为在没有免疫抑制药物的情况下，肝移植比其他同种器官移植更容易被接受。肝脏移植不仅被很好地接受，还可以促使人们再次接受来自同一捐赠者的肾脏或心脏移植，否则这些移植会被拒绝。然而，肝脏这种诱导无反应的能力可能会让一些病毒持续存在，特别是乙肝和丙型肝炎。由于免疫系统无法清除病毒，每五名丙型肝炎患者中就有四人发展为慢性病。尽管已知白细胞进入肝脏并变得无反应，但对阻止有效反应的机制知之甚少。中央情报局S的工作一直走在肝脏免疫学和移植的前沿，他展示了肝脏的结构和血管系统，以及在其中发生的独特细胞相互作用的类型，对于了解其独特的免疫学特性至关重要。利用CIB S独特的啮齿动物实体器官移植方案，我们将为在肝脏遇到抗原后非常早期发生的新机制提供证据。我们建议使用具有良好特征的转基因小鼠模型和先进的分析技术来揭示这一机制。我们将确定这一机制在肝移植中的作用。我们的初步数据表明，成功的可能性非常高。该项目将对移植研究以及食物过敏、慢性丙型肝炎和其他免疫介导性肝病的开发和治疗具有重要意义。

The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Poor responses can be beneficial in a transplantation setting because, in the absence of immunosuppressive drugs, liver transplants are more readily accepted than other organ allografts. Not only are liver transplants well accepted, they can induce secondary acceptance of kidney or heart grafts from the same donor that would otherwise be rejected. However, this ability of the liver to induce unresponsiveness may allow some viruses to persist, particularly , Hepatitis B and C. Four in every five patients infected with hepatitis C develop a chronic disease due to the inability of the immune system to clear the virus. Although it is known that white blood cells enter the liver and become unresponsive, little is known about the mechanisms that prevent an effective response. The CIA s work has been at the forefront of liver immunology and transplantation by demonstrating that the architecture and vasculature of the liver, and therefore the type of unique cellular interactions taking place within it, are essential to gain an understanding of its unique immunological properties. Using the CIB s unique protocols for solid-organ transplantation in rodents, we will provide evidence for a new mechanism that occurs at very early stages after antigen encounter in the liver. We propose to unravel this mechanism using well characterised transgenic mouse models and advanced analytical technology. We will determine the role of this mechanism in liver transplantation. Our preliminary data point to a very high chance of success. This project will have important implications for transplantation studies and for the development and treatment of food allergies and chronic hepatitis C and other of immune-mediated liver diseases.