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

移植物长期存活的主要限制之一是需要使用免疫抑制剂（is）药物来防止移植组织的排斥反应，这与肾脏和代谢毒性、感染和恶性肿瘤等严重副作用有关。因此，诱导移植耐受是移植后治疗的最佳方案。临床定义的“操作性”耐受包括在没有IS的情况下持续数年的移植物接受，而没有移植物功能损害。在人类中，肝移植是一种独特的模型来研究手术耐受的获得，因为多达20%的受体可以完全停止使用IS药物来维持正常的肝功能。肝移植中广泛退出IS的一个潜在限制是，几乎50%的受体是慢性丙型肝炎病毒（HCV）感染，这可以改变或破坏获得耐受性的能力。我们建议在此阐明影响肝移植受者耐受获得的hcv诱导免疫反应的分子和细胞成分。此外，我们将验证is -停药会通过促进细胞抗hcv反应导致肝损伤减少的假设。

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.