Memory CD8⁺ T Cells: Innate-Like Sensors and Orchestrators of Protection

Recent findings have revealed roles for systemic and mucosa-resident memory CD8⁺ T cells in the orchestration of innate immune responses critical to host defense upon microbial infection. Here we integrate these findings into the current understanding of the molecular and cellular signals controlling memory CD8⁺ T cell reactivation and the mechanisms by which these cells mediate effective protection in vivo. The picture that emerges presents memory CD8⁺ T cells as early sensors of danger signals, mediating protective immunity both through licensing of cellular effectors of the innate immune system and via the canonical functions associated with memory T cells. We discuss implications for the development of T cell vaccines and therapies and highlight important areas in need of further investigation.