MTB directly regulates human CD4+ T cell activation

MTB 直接调节人类 CD4 T 细胞活化

• 批准号: 8234559
• 负责人: Christina Louise Lancioni
• 金额: $ 11.9万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8234559
• 关键词: MTB; directly; regulates; human; CD4+

DESCRIPTION (provided by applicant): The projects proposed in this mentored career development award will provide the training and experience required to reach my long term career goal to become an independent physician-scientist conducting translational research that explores the dynamic interaction between the human immune system and microbial pathogens. My career development plan combines graduate level course work with careful oversight by my co-mentors and advisory committee to ensure I am provided with the scientific background and guidance necessary to produce hypothesis driven research with rational project design, execution, and data interpretation throughout my career. The academic and scientific community of Case Western Reserve University will provide state-of-the-art environmental resources to support my career goals, as well as the necessary protected time to allow development of my skills as a physician-scientist through didactic course work, educational seminars and conferences, and pursuit of the research aims included in this proposal. The projects proposed under this application "MTB directly regulates human CD4+ T cell activation" introduce the hypothesis that molecules released by cells infected with Mycobacterium tuberculosis (MTB), directly interact with human CD4+ T cells leading to costimulation and upregulation of T cell activation. The preliminary data supporting this hypothesis demonstrate molecules from MTB directly upregulate human CD4+ T cell activation following T cell receptor stimulation. This interaction between MTB and human CD4+ T cells may influence the host's ability to mount an effective adaptive immune response against the pathogen. These observations suggest human CD4+ T cells utilize pattern-recognition-receptors to sense and respond to foreign material, and exploration of this hypothesis will advance the understanding of how pathogens interact with and modulate the human immune response. In addition to defining the consequences of the interaction between the identified MTB molecules and CD4+ T cells, and the receptor mediating the interaction, this project will explore if differences in CD4+ T cell responses to the identified molecules Influence host susceptibility to tuberculosis. RELEVANCE (See instructions): This research will expand the understanding of the human immune response to infection with MTB and contribute to the development of a superior MTB vaccine. By advancing knowledge of how essential components of the human immune system such as T cells interact with a foreign pathogen, this research will contribute to development of novel immunotherapies for a broad range of pathogens.

描述（由申请人提供）：此指导性职业发展奖中提出的项目将提供实现我的长期职业目标所需的培训和经验，即成为一名独立的医师科学家，进行转化研究，探索人类免疫系统之间的动态相互作用和微生物病原体。我的职业发展计划将研究生水平的课程工作与我的共同导师和咨询委员会的仔细监督结合起来，以确保我在整个职业生涯中获得通过合理的项目设计、执行和数据解释进行假设驱动的研究所需的科学背景和指导。凯斯西储大学的学术和科学界将提供最先进的环境资源来支持我的职业目标，以及必要的受保护时间，以便通过教学课程工作发展我作为医师科学家的技能，教育研讨会和会议，以及实现本提案中包含的研究目标。该申请提出的项目“MTB直接调节人类CD4+T细胞活化”引入了这样的假设：感染结核分枝杆菌(MTB)的细胞释放的分子直接与人类CD4+T细胞相互作用，导致T细胞活化的共刺激和上调。支持这一假设的初步数据表明，MTB 分子在 T 细胞受体刺激后直接上调人类 CD4+ T 细胞活化。 MTB 和人类 CD4+ T 细胞之间的这种相互作用可能会影响宿主针对病原体发起有效的适应性免疫反应的能力。这些观察结果表明人类 CD4+ T 细胞利用模式识别受体来感知和响应外来物质，对这一假设的探索将促进对病原体如何与人类免疫反应相互作用并调节人类免疫反应的理解。除了确定已识别的 MTB 分子与 CD4+ T 细胞之间相互作用的后果以及介导相互作用的受体之外，该项目还将探讨 CD4+ T 细胞对已识别分子的反应差异是否会影响宿主对结核病的易感性。相关性（参见说明）：这项研究将扩大对人类对 MTB 感染的免疫反应的了解，并有助于开发优质的 MTB 疫苗。通过增进对人类免疫系统的重要组成部分（例如 T 细胞）如何与外来病原体相互作用的了解，这项研究将有助于开发针对广泛病原体的新型免疫疗法。