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GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity.
- Source :
-
Blood [Blood] 2017 Feb 02; Vol. 129 (5), pp. 630-642. Date of Electronic Publication: 2016 Dec 07. - Publication Year :
- 2017
-
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.<br /> (© 2017 by The American Society of Hematology.)
- Subjects :
- Animals
Autophagy
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes pathology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes pathology
Cell Line, Tumor
Cytomegalovirus isolation & purification
Cytomegalovirus Infections complications
Cytomegalovirus Infections pathology
Female
Graft vs Host Disease complications
Graft vs Host Disease etiology
Graft vs Host Disease pathology
Humans
Interleukin-15 immunology
Leukemia complications
Leukemia pathology
Leukemia therapy
Mice, Inbred BALB C
Mice, Inbred C57BL
Transplantation, Homologous adverse effects
Bone Marrow Transplantation adverse effects
Cytomegalovirus immunology
Cytomegalovirus Infections immunology
Graft vs Host Disease immunology
Immunity, Innate
Killer Cells, Natural immunology
Killer Cells, Natural pathology
Leukemia immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 129
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 27927647
- Full Text :
- https://doi.org/10.1182/blood-2016-08-734020