GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity.
Blood
; 129(5): 630-642, 2017 02 02.
Article
em En
| MEDLINE
| ID: mdl-27927647
ABSTRACT
Allogeneic bone marrow transplantation (allo-BMT) is a curative therapy for hematological malignancies, but is associated with significant complications, principally graft-versus-host disease (GVHD) and opportunistic infections. Natural killer (NK) cells mediate important innate immunity that provides a temporal bridge until the reconstruction of adaptive immunity. Here, we show that the development of GVHD after allo-BMT prevented NK-cell reconstitution, particularly within the maturing M1 and M2 NK-cell subsets in association with exaggerated activation, apoptosis, and autophagy. Donor T cells were critical in this process by limiting the availability of interleukin 15 (IL-15), and administration of IL-15/IL-15Rα or immune suppression with rapamycin could restore NK-cell reconstitution. Importantly, the NK-cell defect induced by GVHD resulted in the failure of NK-cell-dependent in vivo cytotoxicity and graft-versus-leukemia effects. Control of cytomegalovirus infection after allo-BMT was also impaired during GVHD. Thus, during GVHD, donor T cells compete with NK cells for IL-15 thereby inducing profound defects in NK-cell reconstitution that compromise both leukemia and pathogen-specific immunity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Leucemia
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Transplante de Medula Óssea
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Infecções por Citomegalovirus
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Citomegalovirus
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Doença Enxerto-Hospedeiro
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Imunidade Inata
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Austrália