Taken together, our data demonstrate that irradiation-induced lymphopenia promotes effector T-cells survival via IL-15 signaling the STAT5/Bcl-2 pathway, and enhances T-cell memory formation via IL-15 activation of the forkhead box (FOXO)/Eomesodermin (Eomes) memory and ULK1/autophagy-related gene 7 (Atg7) autophagy pathways and the mitochondrial remodeling. Here, ULK1 is linked to lymphopenia.