Defining Memory CD8 T Cell

Abstract

CD8 T cells comprising the memory pool display considerable heterogeneity, with individual cells differing in phenotype and function. This review will focus on our current understanding of heterogeneity within the antigen-specific memory CD8 T cell compartment and classifications of memory CD8 T cell subsets with defined and discrete functionalities. Recent data suggest that phenotype and/or function of numerically stable circulatory memory CD8 T cells are defined by the age of memory CD8 T cell (or time after initial antigen-encounter). In addition, history of antigen stimulations has a profound effect on memory CD8 T cell populations, suggesting that repeated infections (or vaccination) have the capacity to further shape the memory CD8 T cell pool. Finally, genetic background of hosts and history of exposure to diverse microorganisms likely contribute to the observed heterogeneity in the memory CD8 T cell compartment. Extending our tool box and exploring alternative mouse models (i.e., "dirty" and/or outbred mice) to encompass and better model diversity observed in humans will remain an important goal for the near future that will likely shed new light into the mechanisms that govern biology of memory CD8 T cells.

Keywords: CD8 T cell; age of memory; heterogeneity; history of Ag enounters; memory; outbred mice; protection; subsets.

Figure 1

Phenotypic and functional changes within the circulating Ag-specific CD8 T cell pool with time after infection and with additional Ag encounters. Following infection or vaccination, rare naïve CD8 T cells that recognize their cognate Ag robustly proliferate and give rise to an effector CD8 T cell population. Following contraction of the effector pool, memory CD8 T cells are stably maintained at numbers greater than the naïve pool. Upon re-infection or booster vaccination, primary memory CD8 T cells proliferate and generate a secondary effector and memory CD8 T cell pool that is larger in size than the primary memory pool. Properties of cells comprising the Ag-specific CD8 T cell pool, including expression of phenotypic markers and subset representation, ability to traffic to and localize within tissues, ability to execute effector functions, and ability to provide protection against infection with diverse pathogens differ between naïve, effector, and memory CD8 T cells, and among memory CD8 T cells of different age relative to initial Ag-encounter and of different number of Ag-encounters. – symbols indicate reduced quantity or ability, while + symbols indicate increased quantity or ability. ^aVirtual and/or innate memory cells within the naïve CD8 T cell pool are not considered here.