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.