Committed to memory: lineage choices for activated T cells

The mechanisms for the generation of memory T cells and their delineation into heterogeneous subsets remain unknown. The linear model for memory T-cell generation from differentiated effector cells has been favored, although there is evidence that memory T cells can emerge directly from naive T cells undergoing homeostatic expansion and from activated T cells lacking effector functions. Here, we discuss the evidence from diverse studies of memory generation that support a new ‘intersecting pathway’ model for memory T-cell generation in which antigen-driven effector differentiation and homeostasis-driven memory differentiation follow distinct but analogous pathways. Antigen withdrawal during effector differentiation enables intersection with the memory pathway through a pre-memory intermediate, and memory heterogeneity is influenced by homeostasis, migration and persistence in vivo.