Antigen-specific CD4+ T cell responses to influenza

描述（由申请方提供）：本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CD 4 + T细胞应答的功能相关性和发展。增强和操纵CD 4 + T细胞应答的能力对于感染性疾病、癌症和AIDS的免疫治疗具有重要意义。 在本研究中，将使用反向遗传学生成在血凝素或神经氨酸苷酶中插入的1-Ab背景上含有确定的CD 4+表位的流感病毒。 然后，这些病毒将用于使用四聚体染色、细胞内细胞因子染色和ELISPOT分析来表征流感感染的C57 BL/6模型的初级、次级和记忆阶段中抗原特异性CD 4 T细胞的发育、动力学、表型和效应子功能。 这些数据将用于确定流感模型中抗原特异性CD 4 + T细胞的效应机制。 使用转基因T细胞受体小鼠，还将确定CD 4 + T细胞应答的数量和质量对流感原发性和继发性感染的影响。 最后，将检查流感的抗原特异性与无关抗原引发对不同遗传背景的过敏反应的影响。

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.