Decoding Tissue-Residency: Programming and Potential of Frontline Memory T Cells.

Memory T-cell responses are partitioned between the blood, secondary lymphoid organs, and nonlymphoid tissues. Tissue-resident memory T (Trm) cells are a population of immune cells that remain permanently in tissues without recirculating in blood. These nonrecirculating cells serve as a principal node in the anamnestic response to invading pathogens and developing malignancies. Here, we contemplate how T-cell tissue residency is defined and shapes protective immunity in the steady state and in the context of disease. We review the properties and heterogeneity of Trm cells, highlight the critical roles these cells play in maintaining tissue homeostasis and eliciting immune pathology, and explore how they might be exploited to treat disease.