T Cell Response to Listeria Monocytogenes Infection

T 细胞对单核细胞增生李斯特菌感染的反应

• 批准号: 8197086
• 负责人: Leo Lefrancois
• 金额: $ 36.26万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197086
• 关键词: Anatomy; Animal Model; Antigen-Presenting Cells; Attenuated Vaccines; Bacterial Infections; Bacterial Vaccines; CD27 Antigens; CD4 Positive T Lymphocytes; CD8B1 gene; Categories; Cells; Data; Dendritic Cells; Development; Gene Expression; Generations; Genetic; Genetic Programming; Goals; Heating; Imaging technology; Immune response; Immunity; Immunization; Infection; Life; Link; Listeria monocytogenes; Maps; Measures; Mediating; Memory; Molecular Profiling; Mus; Oral; Pattern; Play; Process; Production; Proteins; Publishing; Recombinants; Reporter; Role; Shapes; Structure; System; T cell response; T memory cell; T-Cell Activation; T-Cell Development; T-Lymphocyte; Testing; Time; Transgenic Organisms; Vaccination; Vaccines; Virulent; Work; base; biodefense; cytokine; gene induction; genetic profiling; killings; mRNA Expression; mutant; novel; pathogen; research study; response; vaccination strategy; vaccine candidate; vaccinology

ABSTRACT The factors essential to induction of a protective immune response to bacterial infections are incompletely understood. In the case of Listeria monocytogenes (LM) infection, a category B Priority Pathogen, CD8 T cells are important in effecting sterilizing immunity. LM interfaces at multiple levels with vaccinology as well as the Biodefense initiative due to the significant potential of LM as a vaccine candidate but also as an agent for intentional contamination and generation of highly virulent recombinant strains. Our work has begun to examine the parameters required for effective immunization with killed or mutant LM as potential vaccine vehicles. Specifically, immunization with heat killed LM (HKL) or irradiated LM (IRL) induced distinct patterns of T cell activation characterized by much more robust CD8 T cell memory induction following vaccination with IRL. However, IRL immunization did not induce the level of T cell activation and memory induction obtained with live LM infection. Thus, this is an excellent system for delineation of the mechanisms involved in promotion of distinct degrees of CD8 T cell activation generated by distinct forms of the same pathogen. Based on our preliminary data, the newly proposed studies focus on integrating the anatomy of effective CD8 T cell immune response initiation and memory T cell reactivation with the costimulatory and genetic programming necessary to drive a protective immune response. The hypothesis that responses induced by live infection versus immunization with attenuated vaccines share common essential components to generate protective memory will be tested in three aims: Specific Aim 1. To determine the role of costimulation and CD4 T cell help in priming and protective recall responses following LM infection or vaccination. Specific Aim 2. To determine the anatomical features of effective CD8 T cell vaccination and recall responses. Specific Aim 3. To define the genetic signature of responding CD8 T cells in response to effective vaccination.

摘要 诱导对细菌感染的保护性免疫应答所必需的因素 并不完全理解。在单核细胞增生李斯特菌（LM）感染的情况下， B类优先病原体，CD8 T细胞在影响杀菌免疫中是重要的。 LM在多个层面与疫苗学以及生物防御计划进行对接， LM作为候选疫苗和治疗药物的巨大潜力 故意污染和产生高毒性重组菌株。我们的工作 已经开始检查有效免疫所需的参数， 突变LM作为潜在的疫苗载体。具体来说，热免疫杀死LM (HKL)或照射LM（IRL）诱导的T细胞活化的不同模式， 免疫接种IRL后，CD8 T细胞记忆诱导更强。 然而，IRL免疫不诱导T细胞活化和记忆水平 用肝LM感染获得诱导。因此，这是一个很好的系统， 参与促进不同程度的CD8 T细胞活化的机制 由同一病原体的不同形式产生。根据我们的初步数据， 新提出的研究重点是整合有效的CD8 T细胞免疫的解剖学， 免疫应答的启动和记忆T细胞的再激活与共刺激和遗传 这是驱动保护性免疫反应所必需的编程。的假设 活感染与减毒疫苗免疫诱导的应答 生成保护性记忆的常见基本组件将在三个方面进行测试 目的： 具体目标1。为了确定共刺激和CD4 T细胞帮助在 LM感染或疫苗接种后的启动和保护性回忆反应。 具体目标2。为了确定有效CD8 T细胞的解剖特征， 疫苗接种和召回反应。 具体目标3。为了确定应答性CD8 T细胞的遗传特征， 有效的疫苗接种。