The antigen-specific CD8 + T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion

Catherine Haluszczak, Adovi D. Akue, Sara E. Hamilton, Lisa D.S. Johnson, Lindsey Pujanauski, Lenka Teodorovic, Stephen C. Jameson, Ross M. Kedl

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

Abstract

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 homeo- static 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-γ 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.

Original languageEnglish (US)
Pages (from-to)435-448
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number2
DOIs
StatePublished - Feb 16 2009

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