The precursors of CD8(+) tissue resident memory T cells: from lymphoid organs to infected tissues

CD8(+) tissue resident memory T cells (T-RM cells) are essential for immune defence against pathogens and malignancies, and the molecular processes that lead to T-RM cell formation are therefore of substantial biomedical interest. Prior work has demonstrated that signals present in the inflamed tissue micro-environment can promote the differentiation of memory precursor cells into mature T-RM cells, and it was therefore long assumed that T-RM cell formation adheres to a 'local divergence' model, in which T-RM cell lineage decisions are exclusively made within the tissue. However, a growing body of work provides evidence for a 'systemic divergence' model, in which circulating T cells already become preconditioned to preferentially give rise to the T-RM cell lineage, resulting in the generation of a pool of T-RM cell-poised T cells within the lymphoid compartment. Here, we review the emerging evidence that supports the existence of such a population of circulating T-RM cell progenitors, discuss current insights into their formation and highlight open questions in the field. CD8(+) tissue resident memory T cells (T-RM cells) are essential for defence against pathogens and malignancies. Prior work had indicated that these cells form within inflamed tissue, but there is emerging evidence that a pool of T-RM cell precursors exists within the circulation. This Review examines the processes and signals within the lymphoid compartment that determine lineage decisions towards the formation of T-RM cells.

Automated summary

CD8(+) tissue resident memory T cells are crucial for immune defence against pathogens and malignancies. While it was previously believed that these cells formed locally within inflamed tissue, emerging evidence suggests the existence of circulating T-RM cell precursors. This review discusses the formation of T-RM cells and the signals within the lymphoid compartment that influence their lineage decisions.