Vascular Endothelium Directs the Development of Regulatory T Cells

候选人目标和职业发展计划：候选人是一名心胸外科医生，具有长期的 长期目标是成为一个学术医疗中心的独立调查员。这位候选人有 学习基础免疫学研究技能，特别关注移植免疫学。这 该奖项将提供所需的支持，以发展成功所需的知识和技能的基础， 长期调查。该基金会将在拟议的五年内通过以下方式建立：（1） 了解血管内皮细胞如何诱导同种异体调节性CD4+ T细胞，（2）了解 先天免疫反应的激活如何影响这一过程，（3）获得关于 免疫调节和先天免疫和（4）收集数据，用于开发一个独立的 一个项目，旨在制定一种特殊的方法， 关注肺移植 环境：圣路易斯华盛顿大学的环境丰富， 一般免疫学。候选人的赞助商是国内和国际公认的独立 在先天免疫和抗原呈递方面有专长研究者。申请人的共同担保人是 世界著名的肺移植外科医生，他也是公认的独立研究者， 同种异体肺移植缺血再灌注损伤。候选人拥有设备齐全的实验室和全职 研究技术员，其工资由该部门提供。 研究提案：该拨款提案的主要目的是研究免疫学 血管内皮和同种异体CD4+ T淋巴细胞之间相互作用的结果。 初步数据表明，CD4+ T淋巴细胞在共培养后获得菌株特异性调节功能 同种异体血管内皮细胞。我们计划确定这种诱导的机制， 具有调节特性的CD4+ T淋巴细胞。此外，我们将研究他们的一代和他们的 在我们的实验室中已经很好地描述了体内模型中的调节特性。最后，初步 数据表明，先天免疫系统的激活可能会破坏CD4* T细胞的诱导， 血管内皮细胞的调节特性。我们计划研究先天性免疫系统的影响 激活这个过程。

Candidate Goals and Career Development Plan: The candidate is a cardiothoracic surgeon with the long- term goal of becoming an independent investigator in an academic medical center. The candidate has learned skills in basic immunological research with a special focus on transplantation immunology. This award will provide support needed to develop the foundation of knowledge and skills required for successful long-term investigation. This foundation will be built over the proposed five years of the award by (1) understanding how vascular endothelial cells induce allogeneic regulatory CD4+ T cells, (2) understanding how activation of innate immune responses influences this process, (3) acquiring detailed knowledge about immune regulation and innate immunity and (4) gathering data for the development of an independent project in developing strategies to induce immunological tolerance to solid organ grafts with a particular focus on lung transplantation. Environment: The environment at Washington University in St. Louis is rich in the availability of expertise in immunology in general. The candidate's sponsor is a nationally and internationally recognized independent investigator with expertise in innate immunity and antigen presentation. The applicant's co-sponsor is a world-renowned lung transplant surgeon, who is also well recognized as an independent investigator in ischemia-reperfusion injury of lung allografts. The candidate has a well-equipped laboratory and a full-time research technician whose salary is supported by the Department. Research Proposal: The primary aim of this grant proposal is to investigate the immunological consequences of interactions between vascular endothelium and allogeneic CD4+ T lymphocytes. Preliminary data indicate that CD4+ T lymphocytes acquire strain-specific regulatory function after co-culture with allogeneic vascular endothelial cells. We plan to identify the mechanism underlying this induction of CD4+ T lymphocytes with regulatory properties. Furthermore, we will examine their generation and their regulatory properties in in vivo models that have been well described in our laboratory. Finally, preliminary data suggest that activation of the innate immune system may disrupt the induction of CD4* T cells with regulatory properties by vascular endothelial cells. We plan to study the impact of innate immune system activation on this process.