*Purpose: The newly identified tissue resident subset of memory T cells (T_RM) provides immune surveillance in the tissue and first response against infections. They are functionally, transcriptionally, and phenotypically distinct from circulating effector and central memory T cells. The role of T_RM in transplantation is unknown. In this study, we investigated the formation and function of T_RM in a mouse kidney transplantation model.

*Methods: Syngeneic B6 or allogeneic (B6xBALB/c) F1.ova kidneys were transplanted to B6 recipients and 1 million OT-I effector T cells were transferred on day 2. Grafts, blood, bone marrow, SLO, and non-lymphoid tissues were harvested 4 and 8 wks after transplantation. Serum creatinine was measured using i-Stat analyzer. T_RM were identified phenotypically as CD44^hiCD62L^lowCD69⁺ CD103^+/- cells after excluding in vivo labeled T cells. Transcriptional characterization of OT-I and polyclonal T_RM using scRNAseq is ongoing. we tested T_RM residency in the graft by performing parabiosis between 4-wk transplanted CD45.1 B6 mice that contained OT-I effectors and CD45.2 B6 parabionts that had received F1.ova kidneys but no OT-I. Whether T_RM are sufficient for rejection is being tested in a re-transplantation model using splenectomized LTBR-/- mice as secondary recipients of F1.ova grafts containing T_RM.

*Results: Mean serum creatinine (mg/dl) was significantly higher in allogeneic vs syngeneic group at wk8 (0.25 vs 0.24 and 0.2 vs 0.8 at 4 & 8 wks, respectively, p<0.05). Graft histology showed mixed acute and chronic rejection in the allogeneic group. Flow analysis of allograft cells demonstrated presence of T_RM cells among OT-I and endogenous T cell populations at 4 & 8 wks. The OT-I population was exclusively T_RM phenotype and was not detected anywhere else. There was no significant difference between mean number of OT-Is’ at wk 4 and wk 8 (125k vs 79k, p=0.94). OT-I T cells could not be detected in the parabionts’ kidney grafts 2 – 4 wks after parabiosis despite equilibration of T cells in the blood, indicating that the T_RM did not re-circulate.

*Conclusions: Our findings reveal that donor-specific T_RM form after transplantation and may contribute to acute and chronic rejection.

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