Fetal and adult progenitors give rise to unique populations of CD8+ T cells

Neonatal CD8+ T cells are unable to form long-lived memory cells in response to infection due to cell-intrinsic reasons; however, the underlying basis for this difference is unclear. Here, using intrathymic transfers with fetal and adult progenitor cells, in conjunction with gene expression profiling and functional assays, we demonstrate that because neonatal CD8+ T cells are derived from a distinct progenitor cell population, they behave differently than adult cells from the time they are generated. These progenitor cells have higher Lin28 expression than adult progenitor cells. We found that adult CD8+ T cells generated from progenitor cells with induced Lin28 expression do not form memory cells, similar to neonatal cells. These findings suggest that neonatal and adult CD8+ T cells belong to separate lineages of CD8+ T cells and potentially explains why it is challenging to elicit memory CD8+ T cells in early life. Gene expression analysis of adult and neonatal CD8+ T cells in the thymus, the spleen, and splenic cell subsets (naïve and innate memory). Small RNA analysis of CD8+ T cells expressing exogenous Lin28b.