Abstract
T cells able to control neoplasia or chronic infections display a signature gene expression profile similar or identical to that of central memory T cells. These cells have qualities of self-renewal and a plasticity that allow them to repeatedly undergo activation (growth, proliferation, and differentiation), followed by quiescence. It is these qualities that define the ability of T cells to establish an equilibrium with chronic infectious agents, and also preserve the ability of T cells to be re-activated (by checkpoint therapy) in response to malignant cancers. Here we describe distinctions between the forms of inhibition mediated by tumors and persistent viruses, we review the properties of T cells associated with long-term immunity, and we identify the transcription factor, FOXO1, as the control point for a program of gene expression that allows CD8(+) T cells to undergo serial reactivation and self-renewal.