Tissue-resident memory T cells in organ transplantation: implications for immune homeostasis and graft outcomes

Tissue-resident memory T cells (TRMs) are a non-circulating subset of memory T cells that reside long-term in peripheral tissues. Once considered passive sentinels, TRMs are now recognized as active regulators of transplant immunity. This review summarizes their phenotypic and functional characteristics across key transplanted organs, including kidney, liver, lung, intestine, skin, and heart. Depending on their activation state and microenvironment, TRMs can promote rejection and modulate local immune balance. Advances in single-cell and spatial profiling have revealed TRM heterogeneity, donor–recipient dynamics, and distinct transcriptional programs. We also highlight therapeutic targets such as NKG2D, IL-15, RORγt, and PD-1, and discuss their potential as biomarkers and immunomodulatory tools. Understanding TRMs as both drivers and regulators of alloimmunity offers new strategies for improving transplant outcomes.