Virtual Memory T Cell Development and Responses In Vivo

描述(申请人提供)：项目总结。记忆性T细胞在许多可测量的方面优于原始T细胞。大多数研究都集中在研究由抗原刺激产生的记忆细胞。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细胞谱系，并在这个池中找到了记忆样T细胞的证据。这些细胞带有典型的细胞表面标志，这些细胞经历了动态平衡扩张，而不是抗原驱动的扩张。因此，未激发的动物含有抗原特异性的CD8T细胞，表达记忆细胞的表型和功能特征。我们认为这是第一次证明这一群体包括对标称外源抗原具有特异性(和反应性)的细胞，并且这些细胞完全参与了对此类抗原的反应过程。我们创造了术语虚拟记忆细胞来指这些记忆表型T细胞，特定于标称抗原，存在于未启动的T细胞库中。这些研究的目的是确定这些虚拟记忆细胞在正常宿主中产生的机制，这些细胞拥有的功能的多样性，以及这些细胞影响和潜在地主导细胞免疫发展的程度。除了更好地理解基础免疫学的意义外，控制或操纵未启动宿主内虚拟记忆细胞的任何记忆样功能的能力很可能导致疫苗接种方法能够在目前所需时间的一小部分内产生保护性的初级T细胞反应。本申请中描述的研究将确定虚拟记忆CD8+T细胞的来源，以及它们在疫苗接种和感染挑战中对效应者和记忆群体的贡献。

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.