Integrating resident memory into T cell differentiation models

Advances in the field of T cell memory, including the discovery of tissue residency, continue to add to the list of defined T cell subsets. Here, we briefly review the role of resident memory T cells (T_RM) in protective immunity, and propose that they exhibit developmental and migrational plasticity. We discuss T cell classification, the concept of cell type versus ‘subset’, and the difficulty of inferring developmental relationships between cells occupying malleable differentiation states. We propose that popular subsetting strategies do not perfectly define boundaries of developmental potential. We integrate T_RM into a ‘terrace’ model that classifies memory T cells along a continuous axis of decreasing developmental potential. This model also segregates cells on the basis of migration properties, although different migration properties are viewed as parallel differentiation states that may be permissive to change.