Tissue-resident T cells, in situ immunity and transplantation

T cells coordinate rejection of transplanted allografts and are key targets for depletion, immunosuppression, and tolerance induction to promote long-term graft survival. Studies in mouse models and humans generally focus on circulating T cells or those from lymphoid sites; however, vast numbers of T cells reside in multiple peripheral tissue sites including lungs, intestines, liver, and skin as non-circulating, tissue-resident memory T cells (Trm cells). In this review, we define the basic properties of Trm cells, the emerging evidence of their importance for protective immunity, and the potential role of resident versus circulating T cells in transplant rejection and in providing protection to prevalent infections posttransplantation. We also discuss potential susceptibilities and/or resistance of protective Trm to immunosuppression therapies, and how consideration of Trm, their compartmentalization, and specificity can enable improved therapies for targeted inhibition of pathogenic and preservation of protective T-cell subsets.