Lin28b reprograms adult CD8⁺T cells to behave more like neonatal cells. (A) Schematic of experimental design: congenic gBT-I adult (Thy1.1) and iLin28b gBT-I adult (Thy1.2) BM cells were transferred into lethally irradiated congenic WT recipient mice (CD45.1) separately. Lin28b expression was induced by DOX in drinking water. Eight weeks later, splenic donor CD8⁺ T cells were sorted and adoptively cotransferred into congenic WT recipient mice (CD45.1). These recipients were infected with 5 × 10³ WT LM-gB and serially bled to examine CD8⁺ T-cell responses. (B-D) Naïve phenotypes of gBT-I WT or gBT-I iLin28b CD8⁺ T cells before adoptive cotransfer. (B) Expression of miRNAs in adult WT gBT-I and adult iLin28b splenic donor CD8⁺ T cells at 8 weeks after reconstitution. (C) Representative plots showing CD44 and CD122 expression by gBT-I BM-derived splenic CD8⁺ T cells 8 weeks after reconstitution. (D) Statistical analysis of the percentages of MP cells from WT gBT-I adult and iLin28b adult CD8⁺ T cells. (E) Relative numbers of iLin28b gBT-I adult (dashed) and WT gBT-I adult (solid) BM-derived donor CD8⁺ T cells postinfection and re-challenge (5 × 10⁴ WT LM-gB); arrows indicate days of infections. (F) Percentages of gBT-I adult and fetal progenitor-derived donor CD8⁺ T cells that are SLECs and MPECs. Data are representative of 2 experiments (****P < .0001).