Immunological and viral determinants of graft hepatitis C after liver transplantation in the context of novel antiviral therapies (B02)

闭塞性细支气管炎综合征(BOS)所致的慢性排斥反应是制约肺移植远期成功的主要障碍。B3项目使用患者材料和人性化的小鼠模型研究了这些过程。他们发现，肺移植后不久(3周)CD4+FOXP3+CD127-细胞的数量与BOS的后期发展密切相关。由于移植物特异性Tregs在预防移植物排斥反应方面比多特异性Tregs更有效，B3将在人源化的小鼠模型中测试这一方法。他们还将确定肺移植患者的免疫功能(T细胞、NK细胞、DSA)，并监测人源化小鼠模型的实验。此外，他们还将研究NK细胞在肺移植中的作用。最后，他们将测试表达免疫调节细胞因子IL-22的设计NK细胞在人源化小鼠模型中防止BOL发展的有效性。

Chronic graft rejection due to the bronchiolitis obliterans syndrome (BOS) after lung transplantation is a major obstacle limiting the long-term success. Project B3 has investigated these processes using patient material and humanized mouse models. They found that the number of CD4+FOXP3+CD127- cells shortly (3 weeks) after lung transplantation correlated strongly with the later development of BOS. As graft-specific Tregs are more potent in preventing graft rejection as compared to polyspecific Tregs, B3 will test this approach in the humanized mouse model. They will also characterize the immune function (T-, NK cells, DSAs) in lung-transplanted patients and monitor the experiments in humanized mice models. In addition, they will investigate the role of NK cells in lung transplantation. Finally, they will test the efficacy of designer NK cells expressing the immunomodulatory cytokine IL-22 to prevent BOL development in the humanized mouse models.