Neonatal CD8+ T cells provide innate immune protection against unrelated pathogens

Abstract

Abstract We previously found that neonatal and adult CD8+ T cells adopt different fates after infection with specific pathogens because they are derived from a distinct progenitor cell that is distinguished by expression of Lin28b. In this report, we investigated if CD8+ T cells respond differently to unrelated pathogens in early life. To start, we compared gene expression profiles of neonatal and adult CD8+ T cells after stimulation with innate cytokines (IL-12 + IL-18). Interestingly, we found that neonatal CD8+ T cells are more responsive and express a distinct cytokine profile compared to their adult counterparts. To examine the biological significance of these age-related differences, we next adoptively transferred monoclonal populations of neonatal or adult CD8+ T cells into T cell-deficient recipients and compared their ability to mediate immune protection against an irrelevant strain of Listeria monocytogenes. Surprisingly, we found that neonatal donor cell displayed increased proliferation and effector functions, and the pathogen burden was significantly reduced when compared to recipients containing adult donor cells. We also found that Lin28b may be responsible for the enhanced responsiveness to innate cytokines in early life, as ectopic expression of Lin28b in adult cells enabled them to initiate a program of bystander activation that was analogous to neonates. Collectively, these findings indicate that neonatal CD8+ T cells possess innate-like functions during infections at the cost of generating memory, and these unique behaviors may be driven by high levels of Lin28b. We currently are employing ATAC-seq to determine whether Lin28b changes the program of bystander activation by altering the chromatin landscape.