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Antigen-inexperienced memory CD8+ T cells: where they come from and why we need them

Abstract

Memory-phenotype CD8+ T cells exist in substantial numbers within hosts that have not been exposed to either foreign antigen or overt lymphopenia. These antigen-inexperienced memory-phenotype T cells can be divided into two major subsets: 'innate memory' T cells and 'virtual memory' T cells. Although these two subsets are nearly indistinguishable by surface markers alone, notable developmental and functional differences exist between the two subsets, which suggests that they represent distinct populations. In this Opinion article, we review the available literature on each subset, highlighting the key differences between these populations. Furthermore, we suggest a unifying model for the categorization of antigen-inexperienced memory-phenotype CD8+ T cells.

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Figure 1: A model of the development of innate memory and virtual memory T cells.
Figure 2: The influence of cytokine complexes on naive and memory CD8+ T cell subsets.

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Acknowledgements

The authors wish to thank C. Suhr, S. Jameson and D. Hildeman for their helpful communications. This work was funded by US National Institutes of Health grants AI101205 and AI066121.

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Correspondence to Ross M. Kedl.

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White, J., Cross, E. & Kedl, R. Antigen-inexperienced memory CD8+ T cells: where they come from and why we need them. Nat Rev Immunol 17, 391–400 (2017). https://doi.org/10.1038/nri.2017.34

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