The fellowship of regulatory and tissue-resident memory cells

T cells located in non-lymphoid tissues have come to prominence in recent years. CD8⁺ tissue-resident memory (Trm) cells are important for tissue immune surveillance, provide an important line of defence against invading pathogens and show promise in cancer therapies. These cells differ in phenotype from other memory populations, are adapted to the tissue they home to where they found their cognate antigen and have different metabolic requirements for survival and activation. CD4⁺ Foxp3⁺ regulatory T (Treg) cells also consist of specialised populations, found in non-lymphoid tissues, with distinct transcriptional programmes. These cells have equally adapted to function in the tissue they made their home. Both Trm and Treg cells have functions beyond immune defence, involving tissue homeostasis, repair and turnover. They are part of a multicellular communication network. Intriguingly, occupying the same niche, Treg cells are important in the establishment of Trm cells, which may have implications to harness the immune surveillance and tissue homeostasis properties of Trm cells for future therapies.