Significance
Enhancing the generation and function of memory T cells represents a crucial strategy to improve protective immunity against pathogens and tumors. The signaling pathway via mechanistic target of rapamycin (mTOR) has been implicated in the regulation of the differentiation of effector and memory T cells, but the upstream regulators or downstream mechanisms remain unclear. In this study, we provide insight into the mechanistic basis that controls mTOR signaling and memory T-cell responses. The deficiency of tuberous sclerosis 1 (Tsc1) in antigen-experienced T cells impairs the differentiation of memory T-cell precursors and the formation of memory T cells, associated with excessive mTOR activity and dysregulated cell metabolism. Our study establishes a molecular mechanism that links mTOR signaling and cell metabolism for memory T-cell development.