Influence of Hepatitis C Virus driven immune responses on the acquisition of operational tolerance in liver transplant recipients

丙型肝炎病毒驱动的免疫反应对肝移植受者操作耐受性获得的影响

• 批准号: 113724503
• 负责人: Dr. Felix Mark Bohne
• 金额: --
• 依托单位: Institut für Virologie (VIRO)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/113724503?language=en
• 关键词: Influence; Hepatitis; Virus; driven; immune

One of the major constraints of long-term graft survival is the need to administer immunosuppressant (IS) drugs to prevent rejection of transplanted tissue, which is associated with severe side effects like renal and metabolic toxicity, infection and malignancies. Therefore, induction of transplantation tolerance constitutes the optimal solution for post transplantation treatment. Clinically defined “operational” tolerance comprises graft acceptance sustained for years in the absence of IS without functional graft impairment. In humans, liver transplantation represents a unique model to investigate the acquisition of operational tolerance, given that up to 20% of recipients can completely discontinue IS drugs maintaining normal liver function. A potential limitation to widespread withdrawal of IS in liver transplantation is the fact that almost 50% of recipients are chronically infected with Hepatitis C Virus (HCV) which can alter or break the ability to attain tolerance. We propose here to elucidate the molecular and cellular components of HCV-induced immune responses influencing tolerance acquisition in liver transplant recipients. In addition we will test the hypothesis that IS-withdrawal will lead to decreased liver damage by promoting cellular anti-HCV-responses.

移植物长期存活的主要限制之一是需要施用免疫抑制剂（IS）药物以防止移植组织的排斥，这与严重的副作用如肾和代谢毒性、感染和恶性肿瘤相关。因此，诱导移植耐受构成了移植后治疗的最佳解决方案。临床定义的“操作”耐受包括在没有IS的情况下持续多年的移植物接受，而没有功能性移植物损伤。在人类中，肝移植是研究获得手术耐受性的独特模型，因为高达20%的受体可以完全停用IS药物，维持正常肝功能。在肝移植中广泛停用IS的一个潜在限制是，几乎50%的受体慢性感染丙型肝炎病毒（HCV），这可能改变或破坏获得耐受的能力。我们建议在这里阐明HCV诱导的免疫反应的分子和细胞成分，影响肝移植受者的耐受性收购。此外，我们将测试的假设，即是撤出将导致减少肝损伤，促进细胞抗HCV反应。