title: Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model.
abstract: 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.
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.|Department of Thoracic Surgery, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sakurada
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshikawa
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000502:physiology; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D014132:Trachea / Q000637:transplantation*; D016042:Transplantation, Heterotopic / Q000009:adverse effects*
chemical_list: D018398:Homeodomain Proteins; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; C064658:RAG-1 protein
keywords: basic (laboratory) research/science; bronchiolitis obliterans (BOS); lung transplantation/pulmonology; natural killer (NK) cells/NK receptors