title: Cytokine complex-expanded natural killer cells improve allogeneic lung transplant function via depletion of donor dendritic cells.
abstract: BACKGROUND
  Natural killer (NK) cells are innate lymphocytes that target virus-infected and tumor cells. Much less is known about their ability to limit adaptive immune responses.
  
  
  OBJECTIVE
  Thus, we investigated to what extent NK cells can influence mouse lung allograft rejection.
  
  
  METHODS
  For this purpose, we employed an orthotopic lung transplantation model in mice.
  
  
  RESULTS
  We demonstrate here that NK cells infiltrate mouse lung allografts before T cells and thereby diminished allograft inflammation, and that NK-cell deficiency enhanced allograft rejection. In contrast, expansion of recipient NK cells through IL-15/IL-15Rα complex treatment resulted in decreased T-cell infiltration and alloreactive T-cell priming as well as improved function of the allogeneic lung transplant. Only perforin-competent, but not perforin-deficient, NK cells were able to transfer these beneficial effects into transplanted NK cell-deficient IL-15Rα(-/-) mice. These NK cells killed allogeneic dendritic cells (DCs) in vitro and significantly decreased the number of allogeneic DCs in transplanted lungs in vivo. Furthermore, DC-depleted lung allografts presented decreased signs of rejection.
  
  
  CONCLUSIONS
  These results suggest that NK cells favor allograft acceptance by depleting donor-derived DCs, which otherwise would prime alloreactive T-cell responses. Thus, conditioning regimens that augment NK-cell reactivity should be clinically explored to prepare lung allograft recipients.
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jungraithmayr
authors.forename: Laura
authors.initials: L
authors.lastname: Codarri
authors.forename: Gregory
authors.initials: G
authors.lastname: Bouchaud
authors.forename: Carsten
authors.initials: C
authors.lastname: Krieg
authors.forename: Onur
authors.initials: O
authors.lastname: Boyman
authors.forename: Gabor
authors.initials: G
authors.lastname: Gyülvészi
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D000818:Animals; D003713:Dendritic Cells; D006084:Graft Rejection / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology*; D051379:Mice; D053647:Receptors, Interleukin-15 / Q000276:immunology
chemical_list: C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15