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¹ Integrated Department of Immunology, University of Colorado Health Science Center, Denver, CO 80045
² Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455

CORRESPONDENCE Ross M. Kedl: ross.kedl{at}uchsc.edu OR Stephen C. Jameson: james024{at}umn.edu

Memory T cells exhibit superior responses to pathogens and tumors compared with their naive counterparts. Memory is typically generated via an immune response to a foreign antigen, but functional memory T cells can also be produced from naive cells by homeostatic mechanisms. Using a recently developed method, we studied CD8 T cells, which are specific for model (ovalbumin) and viral (HSV, vaccinia) antigens, in unimmunized mice and found a subpopulation bearing markers of memory cells. Based on their phenotypic markers and by their presence in germ-free mice, these preexisting memory-like CD44^hi CD8 T cells are likely to arise via physiological homeostatic proliferation rather than a response to environmental microbes. These antigen-inexperienced memory phenotype CD8 T cells display several functions that distinguish them from their CD44^lo counterparts, including a rapid initiation of proliferation after T cell stimulation and rapid IFN- production after exposure to proinflammatory cytokines. Collectively, these data indicate that the unprimed antigen-specific CD8 T cell repertoire contains antigen-inexperienced cells that display phenotypic and functional traits of memory cells.

Abbreviations used: BFA, brefeldin A; gB, glycoprotein B; GF, germ free; HP, homeostatic proliferation; SPF, specific pathogen free; VM, virtual memory.

© 2009 Haluszczak et al.
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