Virtual Memory T Cell Development and Responses In Vivo

描述（由申请人提供）：项目摘要。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，我们已经研究了抗原特异性T细胞库从未免疫的小鼠，并发现记忆样T细胞在这个池的证据。这些细胞带有经历稳态扩增而不是抗原驱动扩增的细胞的典型表面标志物。因此，未致敏的动物含有表达记忆细胞的表型和功能特征的抗原特异性CD8 T细胞。我们认为这是第一次证明，该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针对此类抗原的应答过程。 我们创造了术语虚拟记忆细胞来指代这些记忆表型T细胞，其对名义抗原具有特异性，存在于未引发的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，这些细胞所具有的功能的多样性，以及这些细胞影响和潜在支配细胞免疫发展的程度。除了对基础免疫学有更好的理解外，控制或操纵未致敏宿主内虚拟记忆细胞的任何记忆样功能的能力可能会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细胞应答。本申请中描述的研究将确定虚拟记忆CD8 + T细胞的起源及其对响应疫苗接种和感染性攻毒的效应和记忆群体的贡献。

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.