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.