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Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model
Author(s) -
Kawakami T.,
Ito K.,
Matsuda Y.,
Noda M.,
Sakurada A.,
Hoshikawa Y.,
Okada Y.,
Ogasawara K.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14257
Subject(s) - bronchiolitis obliterans , nkg2d , perforin , immunology , medicine , cd8 , natural killer cell , transplantation , cytotoxic t cell , lung transplantation , biology , immune system , in vitro , biochemistry
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 CD 8 + 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‐ NK 1.1 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 NKG 2D‐ligand in allografts and demonstrated the significance of this using grafts expressing Rae‐1, a murine NKG 2D‐ligand, which induced severe bronchiolitis obliterans in WT and Rag‐1 KO recipients. This effect was ameliorated by injection of anti‐ NKG 2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG 2D leads to the development of murine bronchiolitis obliterans.