Cytokine complex-expanded natural killer cells improve allogeneic lung transplant function via depletion of donor dendritic cells.
Am J Respir Crit Care Med
; 187(12): 1349-59, 2013 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-23590269
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 MAINRESULTS:
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Células Asesinas Naturales
/
Trasplante de Pulmón
/
Interleucina-15
/
Rechazo de Injerto
Límite:
Animals
Idioma:
En
Revista:
Am J Respir Crit Care Med
Asunto de la revista:
TERAPIA INTENSIVA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suiza