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

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

Author information

1
Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

Abstract

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.

PMID:
23590269
PMCID:
PMC3734612
DOI:
10.1164/rccm.201209-1749OC
[Indexed for MEDLINE]
Free PMC Article

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