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

Abstract

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.