Abstract
Abstract Chronic allograft injury remains the leading cause of kidney graft loss after transplantation and no-specific therapy currently exist. We have recently demonstrated that NK cells can kill syngeneic tubular epithelial cells (TEC) and participate in kidney ischemia-reperfusion injury. In this study, we investigated the capacity of NK cells to mediate kidney injury in transplantion. C57BL/6 (B6, H-2b) kidneys were transplanted into nephrectomized F1 (B6 x BALB/c, CB6F1) mice. Serum creatinine levels increased from baseline (22+5 uM, n=8) to 38±6 uM (n=6, P<0.001) at 60 days post transplant, demonstrating a clear loss of kidney function. Infiltrates and low grade renal tubular cell injury were consistently present in B6-to-CB6F1transplants suggesting a non T cell pathway. This was supported by results using a B6-Rag-/--to- CB6F1Rag-/- (B6Rag-/-xBALB/cRag-/-) F1 kidney transplant that eliminates T and B cell but not NK cell participation. Similar levels of kidney dysfunction (creatinine: 34+8 uM, n=6, p<0.01) and histological injury were observed 65 days post transplant. Finally depletion of NK cells prevented kidney injury (25±6 vs 34+8 uM in no antibody injection, n=6, p<0.05) as well as improved histology. In conclusion, these data demonstrate for the first time a critical role for NK cells in mediating chronic kidney injury, which is independent of T and B cells. NK cells are newly appreciated and formidable effectors to chronic kidney injury and graft loss.
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