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- W4313373245 abstract "Abstract The role of TRM in transplantation is unknown. In this study, we investigated the formation and function of TRM in a mouse kidney transplantation model. (B6xBALB/c) F1.ova kidneys were transplanted to B6 recipients and 1m OT-I Teff cells transferred on day 2. Graft, blood, bone marrow, SLO, and liver were harvested 4 and 8 wks after transplantation. TRM were identified as CD44hiCD62LlowCD69+ CD103+/− cells after excluding in vivo labeled T cells. OT-I and polyclonal TRM were transcriptionally characterized using scRNAseq. TRM residency was tested by parabiosis and re-transplantation. To further establish a causal relationship between the TRM OT-Is and rejection we depleted them at wk 4 post adoptive transfer using anti-Thy1.1 (250 ug IV per day for 7d). Mean serum creatinine (mg/dl) was significantly higher in allo vs syn group at wk 8 (0.7 vs 0.2, p<0.05). Graft histology showed mixed acute and chronic rejection in the allo group. Flow analysis of allograft cells demonstrated TRM cells among OT-I and endogenous T cell populations at 4 & 8 wks. The OT-I population was exclusively TRM phenotype by flow and scRNAseq, rapidly produced IFNγ upon re-stimulation, and was not detected anywhere else. There was no significant difference in mean number of OT-Is between wk 4 and wk 8 (277K vs 234k, p=0.74). OT-I T cells could not be detected in the parabiont kidney graft or tissues or in the secondary host outside the re-transplanted kidney, indicating that the TRM are indeed resident in the graft and do not re-circulate. Depleting the OT-Is preserved kidney function at wk 8 compared to the non-depleted group (Cr= 0.7 vs 0.2, p<0.05). Our findings show that donor-specific TRM form in kidney allografts, are functional, and contribute to rejection." @default.
- W4313373245 created "2023-01-06" @default.
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- W4313373245 date "2020-05-01" @default.
- W4313373245 modified "2023-09-27" @default.
- W4313373245 title "Formation and function of resident memory t cells in renal allografts" @default.
- W4313373245 doi "https://doi.org/10.4049/jimmunol.204.supp.161.24" @default.
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