Hiding in Plain Sight: Virtually Unrecognizable Memory Phenotype CD8(+) T cells

Virtual memory T (T(VM)) cells are a recently described population of conventional CD8(+) T cells that, in spite of their antigen inexperience, express markers of T cell activation. T(VM) cells exhibit rapid responsiveness to both antigen-specific and innate stimuli in youth but acquire intrinsic antigen-specific response defects in the elderly. In this article, we review how the identification of T(VM) cells necessitates a re-evaluation of accepted paradigms for conventional memory T (T(MEM)) cells, the potential for heterogeneity within the T(VM) population, and the defining characteristics of T(VM) cells. Further, we highlight recent literature documenting the development of T(VM) cells as a distinct CD8(+) T cell lineage as well their biological significance in the context of disease.