Distinct activation programs in naïve and memory CD8 T cells govern progeny stemness and effector persistence (multiome, OT-I. Day 0 as control, Day 7 and Day 12)

However, how prior antigen experience alters T-cell activation programs remains poorly understood. We longitudinally profiled gene expression in naive, central memory, and effector memory CD8+ T cells in response to cognate antigen across multiple models of acute infection.

Naive T cells engaged TOX- and TCF7-centered programs and generated early stem-like central memory precursors. Their initially slow proliferation was followed by rapid expansion and the production of large numbers of effector cells. Central memory T cells rapidly triggered effector and proliferation programs while maintaining a smaller self-renewing population.