. 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.

Public Health Relevance

We have identified a previously unappreciated population of memory phenotype T cells that exists within the repertoire of naive T cells specific for any given antigen. We propose the term Virtual Memory (VM) to describe this novel population of antigen specific T cells within the unprimed T cell repertoire (in computing, virtual memory describes a form of working memory, based on alternative utilization of existing space). The properties of VM cells indicate that a primary CD8+ T cell response, in a previously unprimed host, is actually the collective result of the response of both naive and memory phenotype T cells. We hypothesize that these pre-existing memory-like CD8 T cells represent a novel, additional arm of the immune repertoire capable of participating in the primary immune response, and we propose to determine the mechanism by which these cells develop 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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Cellular and Molecular Immunology - B Study Section (CMIB)
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Kelly, Halonna R
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University of Colorado Denver
Schools of Medicine
United States
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Pennock, Nathan D; Kedl, Justin D; Kedl, Ross M (2016) T Cell Vaccinology: Beyond the Reflection of Infectious Responses. Trends Immunol 37:170-80
Sosinowski, Tomasz; White, Jason T; Cross, Eric W et al. (2013) CD8α+ dendritic cell trans presentation of IL-15 to naive CD8+ T cells produces antigen-inexperienced T cells in the periphery with memory phenotype and function. J Immunol 190:1936-47