Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model

Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell–mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here...

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Veröffentlicht in:American journal of transplantation 2017-09, Vol.17 (9), p.2338-2349
Hauptverfasser: Kawakami, T., Ito, K., Matsuda, Y., Noda, M., Sakurada, A., Hoshikawa, Y., Okada, Y., Ogasawara, K.
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container_end_page 2349
container_issue 9
container_start_page 2338
container_title American journal of transplantation
container_volume 17
creator Kawakami, T.
Ito, K.
Matsuda, Y.
Noda, M.
Sakurada, A.
Hoshikawa, Y.
Okada, Y.
Ogasawara, K.
description Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell–mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti‐NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin‐KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D‐ligand in allografts and demonstrated the significance of this using grafts expressing Rae‐1, a murine NKG2D‐ligand, which induced severe bronchiolitis obliterans in WT and Rag‐1 KO recipients. This effect was ameliorated by injection of anti‐NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans. In a murine heterotopic tracheal transplant model, cytotoxicity of natural killer cells activated through NKG2D plays an important role in the development of bronchiolitis obliterans.
doi_str_mv 10.1111/ajt.14257
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However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti‐NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin‐KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D‐ligand in allografts and demonstrated the significance of this using grafts expressing Rae‐1, a murine NKG2D‐ligand, which induced severe bronchiolitis obliterans in WT and Rag‐1 KO recipients. This effect was ameliorated by injection of anti‐NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans. 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Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans. 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Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans. In a murine heterotopic tracheal transplant model, cytotoxicity of natural killer cells activated through NKG2D plays an important role in the development of bronchiolitis obliterans.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>28251796</pmid><doi>10.1111/ajt.14257</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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ispartof American journal of transplantation, 2017-09, Vol.17 (9), p.2338-2349
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subjects Allografts
Animals
basic (laboratory) research/science
Bronchiolitis obliterans
bronchiolitis obliterans (BOS)
Bronchiolitis Obliterans - etiology
Bronchiolitis Obliterans - metabolism
Bronchiolitis Obliterans - pathology
Bronchopneumonia
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell-mediated immunity
Cells, Cultured
Cytotoxicity
Disease Models, Animal
Graft Rejection - etiology
Graft Rejection - metabolism
Graft Rejection - pathology
Homeodomain Proteins - physiology
Immunity, Cellular
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Killer Cells, Natural - pathology
Ligands
Lung transplantation
lung transplantation/pulmonology
Lymphocytes T
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, SCID
natural killer (NK) cells/NK receptors
Natural killer cells
NK Cell Lectin-Like Receptor Subfamily K - metabolism
NKG2 antigen
Perforin
Syngeneic grafts
Trachea - transplantation
Transplantation
Transplantation, Heterotopic - adverse effects
Transplants & implants
Xenografts
title Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model
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