To assess the molecular pathway responsible for enhanced Tm cell formation in lymphopenia, we measured the expression of FOXO1 and Eomes, and demonstrate that in vitro IL-15 Tm cells (compared to IL-2 Te cells) and in vivo transferred T-cells in IL-15 sufficient B6 mice (compared to those in IL-15 deficient mice) indeed up-regulate the expression of FOXO1 and Eomes in an IL-15 dependent manner, indicating that lymphopenia promotes Tm-cell formation via IL-15 activation of the FOXO/Eomes memory pathway for memory programming. Here, IL2 is linked to lymphopenia.