Fig. 1. Models of T_RM cell lineage divergence.

Branching of the CD8⁺ tissue resident memory T cell (T_RM cell) lineage from the circulating T cell lineages can be explained by two models. a | The tissue divergence model postulates that memory precursors within the circulation are equal in their potential to give rise to CD8⁺ circulating memory T cells (T_CIRCM cells) and T_RM cells. Only upon reaching the tissue do cells undergo changes that skew them towards the T_RM cell lineage, whereas those memory precursor T cells that remain in circulation start to differentiate into T_CIRCM cell lineages. b | The systemic divergence model postulates the existence of memory precursors within the circulating T cell pool that are poised to produce the T_RM cell lineage and these cells are superior in giving rise to T_RM cells relative to other circulating memory precursors. Note that these models do not address whether a fraction of cells with reduced T_RM cell-forming potential enter the tissue and later rejoin the circulation.