Characterization of donor and recipient CD8+ tissue-resident memory T cells in transplant nephrectomies

Tissue-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.