Initial T cell frequency dictates memory CD8+ T cell lineage commitment

Memory T cells can be divided into central memory T cell (TCM cell) and effector memory T cell (TEM cell) subsets based on homing characteristics and effector functions. Whether TEM and TCM cells represent interconnected or distinct lineages is unclear, although the present paradigm suggests that TEM and TCM cells follow a linear differentiation pathway from naive T cells to effector T cells to TEM cells to TCM cells. We show here that naive T cell precursor frequency profoundly influenced the pathway along which CD8(+) memory T cells developed. At low precursor frequency, those TEM cells generated represented a stable cell lineage that failed to further differentiate into TCM cells. These findings do not adhere to the present dogma regarding memory T cell generation and provide a means for identifying factors controlling memory T cell lineage commitment.