Allogeneic T cells cause acute renal injury after hematopoietic cell transplantation

•Donor-derived T cells are increased and activated in the kidney after allogeneic hematopoietic cell transplantation (allo-HCT).•Allogeneic immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell damage following allo-HCT. Acute kidney injury (AKI) is a...

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Published inBlood advances Vol. 7; no. 22; pp. 6936 - 6948
Main Authors Miyata, Masahiro, Matsuki, Eri, Ichikawa, Kazunobu, Takehara, Tomohiro, Hosokawa, Yuka, Sekiguchi, Erika, Peltier, Daniel, Reddy, Pavan, Ishizawa, Kenichi, Watanabe, Masafumi, Toubai, Tomomi
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 28.11.2023
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Summary:•Donor-derived T cells are increased and activated in the kidney after allogeneic hematopoietic cell transplantation (allo-HCT).•Allogeneic immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell damage following allo-HCT. Acute 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 (NAG), a marker of tubular injury, was elevated in allogeneic recipients on day 14 after allo-BMT. Donor MHC-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 (NGAL), a marker of acute kidney injury, 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 (CTL) 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 following allo-HCT.
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ISSN:2473-9529
2473-9537
DOI:10.1182/bloodadvances.2023009721