Antigen-specific CD4+ T cell responses to influenza

抗原特异性 CD4 T 细胞对流感的反应

• 批准号: 6936903
• 负责人: Paul G. Thomas
• 金额: $ 4.4万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936903
• 关键词: blood tests; cytokine; disease /disorder model; enzyme linked immunosorbent assay; exo alpha sialidase; genetically modified animals; helper T lymphocyte; hemagglutinin; immunologic memory; influenza; influenzavirus A; laboratory mouse; lung; lymph nodes; parainfluenza virus type 1; postdoctoral investigator; protein structure; recombinant virus; spleen; virus antigen; virus genetics

DESCRIPTION (provided by applicant): The overall goal of this proposal is to better understand the functional relevance and development of antigen-specific CD4+ T cell responses in the mouse model of influenza. The ability to potentiate and manipulate CD4+ T cell responses has important implications for immune therapy in infectious diseases, cancer and AIDS. In this study, influenza viruses containing defined CD4+ epitopes on the 1-Ab background inserted in either the hemagglutinin or neuraminadase will be generated using reverse genetics. These viruses will then be used to characterize the development, kinetics, phenotype and effector function of antigen-specific CD4 T cells in primary, secondary and memory phases of the C57BL/6 model of influenza infection using tetramer staining, intracellular cytokine staining and ELISPOT analyses. These data will be used to determine the effector mechanisms of antigen-specific CD4+ T cells in the influenza model. Using a transgenic T cell receptor mouse, the effect of the quantity and quality of CD4+ T cell responses on influenza primary and secondary infection will also be determined. Finally, the effects of antigen-specific vs. unrelated antigen priming by influenza on allergic responses on different genetic backgrounds will be examined.

描述（由申请人提供）：该提案的总体目标是更好地了解流感小鼠模型中抗原特异性CD4+ T细胞反应的功能相关性和开发。增强和操纵CD4+ T细胞反应的能力对传染病，癌症和艾滋病的免疫治疗具有重要意义。 在这项研究中，将使用反向遗传学产生插入的1-AB背景上的含有定义的CD4+表位的流感病毒。 然后，这些病毒将用于表征抗原特异性CD4 T细胞的发育，动力学，表型和效应子功能，使用四聚体染色，细胞内细胞因子体内和ELISPOT分析的C57BL/6模型的一级，次要和记忆阶段。 这些数据将用于确定流感模型中抗原特异性CD4+ T细胞的效应器机制。 使用转基因T细胞受体小鼠，还将确定CD4+ T细胞反应的数量和质量对流感原发性和继发感染的影响。 最后，将研究流感抗原特异性与无关的抗原启动的影响，这些抗原启动对不同遗传背景的过敏反应。