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

项目概要/摘要 肺移植仍然是许多患者唯一可用的治疗方法， 终末期肺病然而，肺移植后的结果仍然是 比其他器官移植后的情况差得多。目前免疫抑制 肺移植患者的策略基于已成功使用的方案， 其他器官的接受者。然而，这些方法并没有考虑到基本的 对肺移植物和其他常用移植物的免疫反应之间的差异 机关利用新的小鼠肺移植模型，我们发现了对肺移植的耐受性。 肺移植物通过淋巴内免疫细胞的相互作用局部调节， 移植物中新形成的聚集体。据报道， 耐受移植物中的免疫调节回路导致移植物浸润的局部活化， 淋巴细胞，引发排斥反应。本申请提出研究机制如何 肺移植后耐受维持在移植物微环境水平 并将允许开发用于肺移植受者的新疗法。

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.