IL-12/IL-18-preactivated donor NK cells enhance GVL effects and mitigate GvHD after allogeneic hematopoietic stem cell transplantation.
Eur J Immunol
; 48(4): 670-682, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29282719
ABSTRACT
Adoptive transfer of donor NK cells has the potential of mediating graft-versus-leukemia (GVL) effect while suppressing acute graft-versus-host-disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these beneficial effects are limited by the transient function of adoptively transferred NK cells. Previous studies demonstrate that cytokine-induced memory-like NK cells that are preactivated by IL-12, IL-15, and IL-18 have enhanced effector functions and long life span in vivo. Here, we investigated the effects of IL-12/18-preactivated and IL-12/15/18-preactivated donor NK cells on GVL and aGVHD in a murine model of allo-HSCT. We found that both IL-12/18- and IL-12/15/18-preactivated NK cells mediated stronger GVL effect than control NK cells mainly due to their elevated activation/cytotoxicity and sustained proliferative potential. Interestingly, we observed that although both IL-12/18- and IL-12/15/18-preactivated NK cells significantly inhibited severe aGVHD, only the IL-12/18-preactivated NK cells maintained the beneficial effect of donor NK cells on mild aGVHD. The IL-12/15/18-preactivated NK cell infusion accelerated aGVHD in the fully-mismatched mild aGVHD model. Our results demonstrated that IL-12/18-preactivated NK cells displayed sustained and enhanced GVL functions, and could mitigate aGVHD despite the severity of the disease. IL-12/18-preactivated donor NK cell infusion may be an effective and safe adoptive therapy after allo-HSCT.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
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Interleucina-15
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Interleucina-18
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Efecto Injerto vs Leucemia
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Subunidad p35 de la Interleucina-12
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Enfermedad Injerto contra Huésped
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2018
Tipo del documento:
Article
País de afiliación:
China