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

T. Kawakami, K. Ito, Y. Matsuda, M. Noda, A. Sakurada, Y. Hoshikawa, Y. Okada, K. Ogasawara

研究成果: Article査読

6 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2338-2349
ページ数12
ジャーナルAmerican Journal of Transplantation
17
9
DOI
出版ステータスPublished - 09-2017

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 移植
  • 薬理学(医学)

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