CD8 T cell quiescence revisited

Abstract

Naïve T cells are typically considered to be in a default state of quiescence, whereas memory T cells undergo basal proliferation and quickly exhibit effector responses when stimulated. Over the past few years, however, a more complex picture has emerged, with evidence that naïve T cell quiescence is actively enforced, and that heterogeneity among naïve T cells influences their capacity to escape quiescence in response to homeostatic cues. Furthermore, the active state of memory T cells may also be instructed, requiring contact with dendritic cells to avoid reversion to quiescence. Here, we discuss these new findings and propose that there is much more flexibility in the quiescent state of naïve and memory T cells than previously thought.

Figure 1. Models of naïve and memory T cell quiescence

The schematic in (a) represents the conventional model, in which naïve T cells are uniformly quiescent cells, responding to homeostatic cues (including IL-7 and self peptide/MHC) as simple survival signals. Transition to the memory population occurs only through foreign antigen encounter and differentiation through an effector phase (not shown). Memory cells are less quiescent, being maintained in the G1 stage of cell cycle and undergoing basal proliferation in response to IL-15. Panel (b) shows a more current model, illustrating the heterogeneity in both naive and memory pools and the capacity of T cells to move between the quiescent and active states based only on homeostatic signals. The colors of the naïve T cells correlate with CD5 expression levels on mouse naïve CD8 T cells – with CD5low cells represented as blue cells, while purple cells indicate the CD5high pool (which are poised to proliferate and differentiate in response to homeostatic cues). The transcription factor Foxp1 is involved in enforcing quiescence in the naïve CD8 T cell population. In the memory population, regular encounters with Dendritic cells is important for sustaining their maintenance of G₁ phase and functional efficacy.

Figure 1. Models of naïve and memory T cell quiescence

The schematic in (a) represents the conventional model, in which naïve T cells are uniformly quiescent cells, responding to homeostatic cues (including IL-7 and self peptide/MHC) as simple survival signals. Transition to the memory population occurs only through foreign antigen encounter and differentiation through an effector phase (not shown). Memory cells are less quiescent, being maintained in the G1 stage of cell cycle and undergoing basal proliferation in response to IL-15. Panel (b) shows a more current model, illustrating the heterogeneity in both naive and memory pools and the capacity of T cells to move between the quiescent and active states based only on homeostatic signals. The colors of the naïve T cells correlate with CD5 expression levels on mouse naïve CD8 T cells – with CD5low cells represented as blue cells, while purple cells indicate the CD5high pool (which are poised to proliferate and differentiate in response to homeostatic cues). The transcription factor Foxp1 is involved in enforcing quiescence in the naïve CD8 T cell population. In the memory population, regular encounters with Dendritic cells is important for sustaining their maintenance of G₁ phase and functional efficacy.