AbstractTissue-resident memory T (T_RM) cells are characterized by their surface expression of CD69 and can be subdivided in CD103+ and CD103− T_RM cells. The origin and functional characteristics of T_RM cells in the renal allograft are largely unknown. To determine these features we studied T_RM cells in transplant nephrectomies. T_RM cells with a CD103+ and CD103− phenotype were present in all samples (n = 13) and were mainly CD8+ T cells. Of note, donor-derived T_RM cells were only detectable in renal allografts that failed in the first month after transplantation. Grafts, which failed later, mainly contained recipient derived T_RM cells. The gene expression profiles of the recipient derived CD8+ T_RM cells were studied in more detail and showed a previously described signature of tissue residence within both CD103+ and CD103− T_RM cells. All CD8+ T_RM cells had strong effector abilities through the production of IFNγ and TNFα, and harboured high levels of intracellular granzyme B and low levels of perforin. In conclusion, our results demonstrate that donor and recipient T_RM cells reside in the rejected renal allograft. Over time, the donor-derived T_RM cells are replaced by recipient T_RM cells which have features that enables these cells to aggressively respond to the allograft.