Miyata, MasahiroMatsuki, EriIchikawa, KazunobuTakehara, TomohiroHosokawa, YukaSekiguchi, ErikaPeltier, DanielReddy, PavanIshizawa, KenichiWatanabe, MasafumiToubai, Tomomi2024-05-142024-05-142023Miyata M, Matsuki E, Ichikawa K, et al. Allogeneic T cells cause acute renal injury after hematopoietic cell transplantation. Blood Adv. 2023;7(22):6936-6948. doi:10.1182/bloodadvances.2023009721https://hdl.handle.net/1805/40735Acute kidney injury (AKI) is a frequent complication of allogeneic hematopoietic cell transplantation (allo-HCT). There are many causes of AKI after allo-HCT, but it is unknown whether renal acute graft-versus-host disease (aGVHD) caused by direct allogeneic donor T-cell-mediated renal damage contributes. Here, we tested whether allogeneic donor T cells attack kidneys in murine models of aGVHD. To avoid confounding effects of nephrotoxic agents, we did not administer immunosuppressants for GVHD prophylaxis. We found that urinary N-acetyl-β-D-glucosaminidase, a marker of tubular injury, was elevated in allogeneic recipients on day 14 after allogeneic bone marrow transplantation. Donor major histocompatibility complex-positive cells were present and CD3+ T cells were increased in the glomerulus, peritubular capillaries, interstitium, and perivascular areas in the kidneys of allo-HCT recipient mice. These T cells included both CD4+ and CD8+ cells with elevated activation markers, increased exhaustion markers, and greater secretion of proinflammatory cytokines and cytotoxic proteins. Consistent with allo-T-cell-mediated renal damage, expression of neutrophil gelatinase-binding lipocalin, a marker of AKI, and elafin, a marker of aGVHD, were increased in renal tissue of allogeneic recipients. Because apoptosis of target cells is observed on histopathology of aGVHD target tissues, we confirmed that alloreactive T cells increased apoptosis of renal endothelial and tubular epithelial cells in cytotoxic T-lymphocyte assays. These data suggest that immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell injury in allo-HCT recipients and that aGVHD may contribute to AKI after allo-HCT.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalAcute kidney injuryBone marrow transplantationHematopoietic stem cell transplantationArticle