The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion.
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-gamma 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.
Haluszczak
Catherine
C
Integrated Department of Immunology, University of Colorado Health Science Center, Denver, CO 80045, USA.
Akue
Adovi D
AD
Hamilton
Sara E
SE
Johnson
Lisa D S
LD
Pujanauski
Lindsey
L
Teodorovic
Lenka
L
Jameson
Stephen C
SC
Kedl
Ross M
RM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice
C476399:Cd44 protein, mouse; D016207:Cytokines; D018960:Hyaluronan Receptors