Environmental Cues Dictate the Fate of Individual CD8+ T Cells Responding to Infection

Many studies have examined pathways controlling effector T cell differentiation, but less is known about the fate of individual CD8(+) T cells during infection. Here, we examine the antiviral and antibacterial responses of single CD8(+) T cells from the polyclonal repertoire. The progeny of naive clonal CD8(+) T cells displayed unique profiles of differentiation based on extrinsic pathogen-induced environmental cues, with some clones demonstrating extreme bias toward a single developmental pathway. Moreover, even within the same animal, a single naive CD8(+) T cell exhibited distinct fates that were controlled by tissue-specific events. However, memory CD8(+) T cells relied on intrinsic factors to control differentiation upon challenge. Our results demonstrate that stochastic and instructive events differentially contribute to shaping the primary and secondary CD8(+) T cell response and provide insight into the underlying forces that drive effector differentiation and protective memory formation.