Discipline in Stages: Regulating CD8+ Resident Memory T Cells

Resident memory CD8(+) T (T-RM) cells are a lymphocyte lineage distinct from circulating memory CD8(+) T cells. T-RM lodge within peripheral tissues and secondary lymphoid organs where they provide rapid, local protection from pathogens and control tumor growth. However, dysregulation of CD8(+) T-RM formation and/or activation may contribute to the pathogenesis of autoimmune diseases. Intrinsic mechanisms, including transcriptional networks and inhibitory checkpoint receptors control T-RM differentiation and response. Additionally, extrinsic stimuli such as cytokines, cognate antigen, fatty acids, and damage signals regulate T-RM formation, maintenance, and expansion. In this review, we will summarize knowledge of CD8(+) T-RM generation and highlight mechanisms that regulate the persistence and responses of heterogeneous T-RM populations in different tissues and distinct microenvironments.