Abstract
Virtual memory T (TVM) cells are a recently described population of conventional CD8+ T cells that, in spite of their antigen inexperience, express markers of T cell activation. TVM 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 TVM cells necessitates a re-evaluation of accepted paradigms for conventional memory T (TMEM) cells, the potential for heterogeneity within the TVM population, and the defining characteristics of TVM cells. Further, we highlight recent literature documenting the development of TVM cells as a distinct CD8+ T cell lineage as well their biological significance in the context of disease.
Highlights
CD8+ T cells have been considered to exist along a single spectrum; resting naïve CD8+ T (TN) cells, upon recognition of cognate antigen and subsequent activation, differentiate into effector T cells, which contract upon antigen clearance, leaving a conventional memory T (TMEM) cell population
Other groups have shown that overexpression of Eomes alone was sufficient to drive antigen inexperienced cells towards a memory phenotype [89]. These studies solidify the importance of Eomes in TVM cell development, and suggest that these cells represent a distinct lineage of CD8+ T development that is ratified in the periphery through IL-15 exposure [53]
The heightened semi-differentiated phenotype seen in day 1 compared to day 28 TVM cells was associated with an increase in chromatin accessibility at gene loci associated with effector function facilitating rapid transcription
Summary
CD8+ T cells have been considered to exist along a single spectrum; resting naïve CD8+ T (TN) cells, upon recognition of cognate antigen and subsequent activation, differentiate into effector T cells, which contract upon antigen clearance, leaving a conventional memory T (TMEM) cell population. TMEM cells are quiescent but poised for activation, and present at a relatively high antigen-specific frequency. These features of CD8+ T cell memory underpin their ability to respond rapidly after reencounter with the same antigen and are a hallmark of adaptive immunity. The interest in TVM cells stems from their ability to exert robust and rapid effector functions never previously attributed to antigen-inexperienced T cells, their responsiveness to both antigen-specific and innate stimuli, their superior survival capacity and their intrinsic dysfunction in elderly mice and humans [2,3,4,5,6]. We discuss recent advances in our understanding of TVM cells, including their development as a distinct cell lineage and their biological relevance in protection from infection and cancers [7,8,9,10,11]
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