Memory Cell Migration Following Influenza virus Infection

流感病毒感染后的记忆细胞迁移

• 批准号: 7391874
• 负责人: Kimberly D. Klonowski
• 金额: $ 18.44万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7391874
• 关键词: Adoptive Transfer; CD8B1 gene; Cells; Class; Cues; Data; Endothelial Cells; Environment; Epithelial; Equilibrium; Future; Genetic; Goals; Immune response; Immunity; Immunologic Memory; Infection; Inferior; Influenza; Influenza A virus; Interleukin-15; Lung; Lymphocyte; Lymphoid; Mediating; Memory; Nomads; Numbers; Operative Surgical Procedures; Peripheral; Phenotype; Population; Purpose; Recruitment Activity; Refractory; Research; Role; Seeds; Signal Transduction; Site; Source; System; T-Cell Activation; T-Lymphocyte; Time; Tissues; Vaccines; Viral; Virus; Virus Diseases; cell motility; cytokine; design; influenzavirus; memory retention; migration; monolayer; prevent; self-renewal; trafficking; vaccine development

DESCRIPTION (provided by applicant): Understanding how immunological memory is maintained in peripheral tissues such as the lung is pivotal for designing a vaccine against the tissue-specific infection of influenza A. Despite much progress towards understanding how CD8 T cells participate in immune responses against influenza, long-term protection has been difficult to achieve. This is in part due to the decline in number of competent effector memory cells in the lung airways, the portal of viral entry, despite continued recruitment of a secondary pool of memory cells to the lung. The goal of this proposal is to generate an understanding how we can both recruit and sustain migrants in the lung airways to prevent future influenza infections. In Aim 1 we will determine the source of memory cells which seed the lung airways at late time points following infection using both an adoptive transfer system and genetic and surgical manipulation to selectively add or remove populations of memory cells. In Aim 2 we will determine how IL-15 influences the migration and homeostatic proliferation of influenza- specific memory cells in the lung. These studies will place a special emphasis on the interaction between memory cells and lung-specific epithelial and endothelial cells. Whether these cells provide signals, such as IL-15, to induce both trafficking and homestatic proliferation will be explored. Together, these studies will assist in identification of and recruitment of cells which maintain long-term protective CD8 T cell immunity in the lung and will help in the development of vaccines.

描述（由申请方提供）：了解免疫记忆如何在外周组织（如肺）中维持对于设计针对甲型流感组织特异性感染的疫苗至关重要。尽管在理解CD 8 T细胞如何参与流感免疫应答方面取得了很大进展，但长期保护一直难以实现。这部分是由于在肺气道中感受态效应记忆细胞的数量下降，尽管持续募集次级记忆细胞库到肺，但肺气道是病毒进入的门户。该提案的目标是了解我们如何招募和维持肺气道的移民，以预防未来的流感感染。在目标1中，我们将使用过继转移系统以及遗传和手术操作来选择性地添加或去除记忆细胞群，确定在感染后的晚期时间点接种肺气道的记忆细胞的来源。在目标2中，我们将确定IL-15如何影响肺部流感特异性记忆细胞的迁移和稳态增殖。这些研究将特别强调记忆细胞与肺特异性上皮细胞和内皮细胞之间的相互作用。这些细胞是否提供信号，如IL-15，以诱导贩运和稳态增殖将进行探讨。总之，这些研究将有助于识别和招募在肺中维持长期保护性CD 8 T细胞免疫的细胞，并将有助于疫苗的开发。