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: T Kawakami, K Ito, Y Matsuda, M Noda, A Sakurada, Y Hoshikawa, Y Okada, K Ogasawara
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 17 Issue 9 Pg. 2338-2349 (Sep 2017) ISSN: 1600-6143 [Electronic] United States
• PMID: 28251796 (Publication Type: Journal Article)
• Copyright: © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Homeodomain Proteins
• Klrk1 protein, mouse
• NK Cell Lectin-Like Receptor Subfamily K
• RAG-1 protein

Topics

• Animals
• Bronchiolitis Obliterans (etiology, metabolism, pathology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Disease Models, Animal
• Graft Rejection (etiology, metabolism, pathology)
• Homeodomain Proteins (physiology)
• Immunity, Cellular
• Killer Cells, Natural (immunology, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, SCID
• NK Cell Lectin-Like Receptor Subfamily K (metabolism)
• Trachea (transplantation)
• Transplantation, Heterotopic (adverse effects)