Generating diversity: transcriptional regulation of effector and memory CD8 T-cell differentiation

Abstract

In response to acute infections or vaccines, naive antigen-specific CD8(+) T cells proliferate and differentiate into effector cytotoxic lymphocytes that acquire the ability to kill infected cells. While the majority of differentiated effector cells die after pathogen clearance, a small number evade terminal differentiation, downregulate active effector functions, and survive as long-lived, self-renewing memory T cells. Our understanding of how effector CD8(+) T cells adopt these different cell fates has grown greatly in recent years. In this review, we discuss the transcriptional regulators that are known to support general effector differentiation, terminal effector differentiation, and memory cell formation. We propose that the diversity of activated CD8(+) T-cell differentiation states is achieved via gradients of activity or expression of transcriptional regulators that are regulated by the level of inflammation and antigenic signaling the T cells experience during infection.