HP memory cells resemble conventional memory cells in many of their phenotypic and functional traits. 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. 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. 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. 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. 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. Memory T cells exhibit superior responses to pathogens and tumors compared with their naive counterparts.
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