The Role of Lymphoid Neogenesis in the Maintenance of Lung Transplant Tolerance

项目摘要/摘要 对于许多患者来说，肺移植仍然是唯一可用的治疗方法。 死于终末期肺部疾病。然而，肺移植后的结果仍然是 比其他器官移植后的情况严重得多。当前的免疫抑制药 肺移植患者的策略是基于已经成功使用的方案 对于其他器官的接受者。然而，这些方法并没有考虑到根本原因 肺移植与其他常见移植实体免疫反应的差异 器官。利用新的小鼠肺移植模型，我们发现了对 肺移植通过淋巴组织内免疫细胞的相互作用进行局部调节 移植物中新形成的聚集体。我们已经报道了中断 耐受性移植物中的免疫调节回路导致移植物渗透的局部激活 淋巴细胞，这会引发排斥反应。这个应用程序建议研究机制是如何 肺移植后耐受性维持在移植物微环境水平 并将为肺移植接受者开发新的治疗方法。

PROJECT SUMMARY / ABSTRACT Pulmonary transplantation remains the only available treatment for numerous patients, who suffer from end-stage lung disease. However, outcomes after lung transplantation continue to be substantially worse than those after transplantation of other organs. Current immunosuppressive strategies for lung transplant patients are based on protocols that have been successfully used for recipients of other organs. However, such approaches do not account for fundamental differences between immune responses to lung grafts and other commonly transplanted solid organs. Utilizing new mouse models of lung transplantation we have uncovered that tolerance to pulmonary grafts is regulated locally through interactions of immune cells within lymphoid aggregates that are newly formed in the graft. We have reported that disruption of immunoregulatory circuits in tolerant grafts results in the local activation of graft-infiltrating lymphocytes, which triggers rejection. This application proposes to study mechanisms how tolerance is maintained at the level of the graft microenvironment after pulmonary transplantation and will allow for the development of new therapies for lung transplant recipients.