Virtual Memory T Cell Development and Responses In Vivo

体内虚拟记忆 T 细胞的发育和反应

• 批准号: 9023407
• 负责人: Ross M Kedl
• 金额: $ 35.02万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-11 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9023407
• 关键词: Affinity; Animals; Antigens; CD8B1 gene; Cell physiology; Cells; Cellular Immunity; Characteristics; Coin; Data; Development; Event; Exposure to; Family; Future; Generations; Goals; Health; IL2RB gene; Immune; Immune response; Immunity; Immunization; Immunologic Memory; Immunology; In Vitro; Inflammation; Inflammatory; Interferons; Interleukin-15; Interleukin-4; Investigation; Kinetics; Lead; Literature; Measurable; Mediating; Memory; Methods; Mind; Minor; Mus; Nature; Peripheral; Phenotype; Population; Production; Property; Role; Short-Term Memory; Site; Surface; T cell response; T memory cell; T-Cell Development; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Text; Time; Tissues; Ursidae Family; Vaccination; adaptive immunity; arm; base; cell type; clinical application; cytokine; fitness; in vivo; novel; response; trait; transcription factor; vaccination strategy; vaccine development; virtual

DESCRIPTION (provided by applicant): Project summary. Memory T cells are superior to primary T cells in a number of measurable ways. Most studies focus their investigation on studying memory cells resulting from antigenic stimulation. However, using a newly developed experimental method, we have studied the antigen specific T cell repertoire from unimmunized mice and find evidence for memory-like T cells within this pool. These cells bear surface markers typical of cells having undergone homeostatic expansion rather than antigen driven expansion. Thus, unprimed animals contain antigen-specific CD8 T cells expressing phenotypic and functional characteristics of memory cells. We believe this to be the first demonstration that this population includes cells specific for (and reactive to) nominal foreign antigens, and that these cells participate fully in the course of a response against such antigens. We have coined the term Virtual Memory cells to refer to these memory phenotype T cells, specific for nominal antigen, that exist within the unprimed T cell repertoire. The goal of these studies is to determine the mechanism by which these Virtual Memory cells arise within a normal host, the diversity of functions these cells possess, and the degree to which these cells influence, and potentially dominate, the development of cellular immunity. Besides the implications for a greater understanding of basic immunology, the ability to control or manipulate any of the memory-like functions of Virtual Memory cells within an unprimed host may well lead to vaccination methods able to generate, in a fraction of the time currently necessary, a protective primary T cell response. The studies described in this application will determine the origin of Virtual Memory CD8+ T cells and their contribution to the effector and memory populations in response to vaccination and infectious challenge.

描述（由申请人提供）：项目概述。记忆T细胞在许多可测量的方面优于原代T细胞。大多数研究都集中在研究抗原刺激引起的记忆细胞。然而，使用一种新开发的实验方法，我们研究了来自未免疫小鼠的抗原特异性T细胞库，并在该池中发现了记忆样T细胞的证据。这些细胞具有典型的细胞表面标记，这些细胞经历了稳态扩张，而不是抗原驱动的扩张。因此，未引物的动物含有抗原特异性CD8 T细胞，表达记忆细胞的表型和功能特征。我们相信这是第一次证明这个群体包括对名义外来抗原特异性（和反应性）的细胞，并且这些细胞充分参与对这些抗原的反应过程。我们已经创造了术语虚拟记忆细胞，指的是这些记忆表现型T细胞，特异性的名义抗原，存在于未引物的T细胞库。这些研究的目的是确定这些虚拟记忆细胞在正常宿主体内产生的机制，这些细胞所拥有的功能的多样性，以及这些细胞影响和潜在支配细胞免疫发展的程度。除了对基本免疫学有更深入的了解外，在未启动宿主中控制或操纵虚拟记忆细胞的任何类似记忆功能的能力很可能导致疫苗接种方法能够在目前所需的一小部分时间内产生保护性初级T细胞反应。本申请中描述的研究将确定虚拟记忆CD8+ T细胞的起源，以及它们对疫苗接种和感染挑战的效应和记忆群体的贡献。