Cytokine complex-expanded natural killer cells improve allogeneic lung transplant function via depletion of donor dendritic cells

Am J Respir Crit Care Med. 2013 Jun 15;187(12):1349-59. doi: 10.1164/rccm.201209-1749OC.


Rationale: 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.

Objectives: 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.

Measurements and main 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells*
  • Graft Rejection / immunology*
  • Interleukin-15 / immunology*
  • Killer Cells, Natural / immunology*
  • Lung Transplantation / immunology*
  • Mice
  • Receptors, Interleukin-15 / immunology


  • Il15ra protein, mouse
  • Interleukin-15
  • Receptors, Interleukin-15