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

了解肝脏对 T 细胞的快速清除：改善肝移植的关键一步。

• 批准号: nhmrc : 457043
• 负责人: Dr Alex Bishop
• 金额: $ 27.48万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/understanding-rapid-t-liver-transplantation/77082
• 关键词: Understanding; rapid; cell; clearance; liver

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.

肝脏具有自相矛盾的特性：它是对病原体产生有效免疫反应的部位，但在某些情况下，它也会引起无害的免疫反应。不良反应在移植中是有益的，因为在没有免疫抑制药物的情况下，肝移植比其他同种异体器官移植更容易被接受。肝移植不仅被广泛接受，而且可以诱导来自同一供者的肾脏或心脏移植的二次接受，否则这些移植会被排斥。然而，肝脏诱导无反应的这种能力可能会让一些病毒持续存在，特别是乙肝和丙肝。由于免疫系统无法清除病毒，每5个丙肝患者中就有4个发展为慢性疾病。虽然我们知道白细胞进入肝脏后会变得无反应，但对阻止有效反应的机制却知之甚少。中情局的工作一直走在肝脏免疫学和移植的前沿，证明了肝脏的结构和血管系统，以及在肝脏内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独特的啮齿动物实体器官移植方案，我们将为抗原在肝脏遭遇后的早期阶段发生的新机制提供证据。我们建议利用表征良好的转基因小鼠模型和先进的分析技术来解开这一机制。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几率很高。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的肝脏疾病的发展和治疗具有重要意义。