Environmental cues dictate the fate of individual CD8⁺ T cells responding to infection

Many studies have examined pathways controlling effector Tcell differentiation, but less is known about the fate of individual CD8⁺ Tcells during infection. Here, we examine the antiviral and antibacterial responses of single CD8⁺ Tcells from the polyclonal repertoire. The progeny of naive clonal CD8⁺ Tcells 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⁺ Tcell exhibited distinct fates that were controlled by tissue-specific events. However, memory CD8⁺ Tcells 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⁺ Tcell response and provide insight into the underlying forces that drive effector differentiation and protective memory formation.