MTB directly regulates human CD4+ T cell activation

MTB 直接调节人类 CD4 T 细胞活化

• 批准号: 7708329
• 负责人: Christina Louise Lancioni
• 金额: $ 12.66万
• 依托单位: CASE WESTERN RESERVE 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/7708329
• 关键词: Address; Advisory Committees; Affect; Antigens; Arts; CD4 Positive T Lymphocytes; CD8B1 gene; Cell physiology; Cells; Communities; Data; Dendritic Cells; Development; Development Plans; Disease; Ensure; Genes; Genetic Polymorphism; Goals; Human; IL2RA gene; Immune response; Immune system; Immunotherapy; Individual; Infection; Instruction; Investigation; K-Series Research Career Programs; Knowledge; Lipoproteins; Mediating; Memory; Mentors; Mycobacterium tuberculosis; Pathway interactions; Pattern; Pattern recognition receptor; Physicians; Predisposition; Production; Receptor Gene; Receptor Signaling; Recombinants; Recording of previous events; Research; Research Personnel; Research Project Grants; Resources; Scientist; Screening procedure; Signal Pathway; Signaling Pathway Gene; T-Cell Activation; T-Cell Proliferation; T-Cell Receptor; T-Lymphocyte; Time; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-like receptors; Training; Translational Research; Tuberculosis; Tuberculosis Vaccines; Universities; Up-Regulation; Work; career; career development; cytokine; design; experience; interest; macrophage; microbial; novel; pathogen; programs; receptor; response; skills; success; symposium

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）：这个导师职业发展奖中提出的项目将为我提供必要的培训和经验，以实现我的长期职业目标，成为一名独立的医师科学家，进行探索人类免疫系统和微生物病原体之间动态相互作用的转化研究。我的职业发展计划将研究生水平的课程与我的共同导师和咨询委员会的仔细监督相结合，以确保我获得必要的科学背景和指导，以在我的职业生涯中进行合理的项目设计，执行和数据解释的假设驱动研究。凯斯西储大学的学术和科学社区将提供最先进的环境资源来支持我的职业目标，以及必要的保护时间，通过教学课程、教育研讨会和会议，以及追求本提案中包括的研究目标，让我作为一名医生和科学家的技能得到发展。申请项目“MTB直接调控人CD4+ T细胞活化”引入了结核分枝杆菌（MTB）感染细胞释放的分子直接与人CD4+ T细胞相互作用，共同刺激和上调T细胞活化的假设。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细胞的激活。MTB与人类CD4+ T细胞之间的这种相互作用可能影响宿主对病原体进行有效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，探索这一假设将促进对病原体如何相互作用和调节人类免疫反应的理解。除了确定已鉴定的结核分枝杆菌分子与CD4+ T细胞之间相互作用的后果以及介导这种相互作用的受体外，该项目还将探索CD4+ T细胞对已鉴定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（见说明）：这项研究将扩大对人类对结核分枝杆菌感染的免疫反应的认识，并有助于开发一种优良的结核分枝杆菌疫苗。通过进一步了解人体免疫系统的基本组成部分，如T细胞如何与外来病原体相互作用，这项研究将有助于开发针对多种病原体的新型免疫疗法。