Vascular Endothelium Directs the Development of Regulatory T Cells

应聘者目标和职业发展计划：应聘者是一名心胸外科医生，有长期- 学期目标是成为一名学术医学中心的独立研究员。候选人有 基础免疫学研究，特别是移植免疫学方面的学习技能。这 奖励将提供必要的支持，以发展成功所需的知识和技能基础 长期的调查。这一基础将在拟议的五年内由(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以及(4)收集数据用于发展独立的 制定策略以诱导对具有特定免疫耐受的实体器官移植的项目 重点做好肺移植。 环境：圣路易斯华盛顿大学的环境中有丰富的专业知识可用 一般的免疫学。候选人的赞助人是一位国内和国际公认的独立人士 在先天免疫和抗原呈递方面有专业知识的调查员。申请人的共同保荐人是 世界著名的肺移植外科医生，也是公认的独立调查员 同种异体肺移植的缺血再灌注损伤。应聘者有一个设备齐全的实验室和一名全职人员 研究技术员，其工资由部门提供支持。 研究建议：这项拨款建议的主要目的是研究免疫学 血管内皮细胞与同种异体CD4+T淋巴细胞相互作用的后果。 初步数据表明，在共培养后，CD4+T淋巴细胞获得了品系特异性的调节功能 同种异体血管内皮细胞。我们计划确定这种诱导的机制 具有调节功能的CD4+T淋巴细胞。此外，我们将检查他们的一代和他们的 我们实验室已经很好地描述了体内模型中的调节特性。最后，初步的 数据表明，先天免疫系统的激活可能会扰乱CD4*T细胞的诱导 血管内皮细胞的调节特性。我们计划研究先天免疫系统对 在此过程中激活。

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.