GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity

Bunting, Mark D., Varelias, Antiopi, Souza-Fonseca-Guimaraes, Fernando, Schuster, Iona S., Lineburg, Katie E., Kuns, Rachel D., Fleming, Peter, Locke, Kelly R., Huntington, Nicholas D., Blazar, Bruce R., Lane, Steven W., Tey, Siok-Keen, MacDonald, Kelli P. A., Smyth, Mark J., Degli-Esposti, Mariapia A. and Hill, Geoffrey R. (2017) GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity. Blood, 129 5: 630-642. doi:10.1182/blood-2016-08-734020


Author Bunting, Mark D.
Varelias, Antiopi
Souza-Fonseca-Guimaraes, Fernando
Schuster, Iona S.
Lineburg, Katie E.
Kuns, Rachel D.
Fleming, Peter
Locke, Kelly R.
Huntington, Nicholas D.
Blazar, Bruce R.
Lane, Steven W.
Tey, Siok-Keen
MacDonald, Kelli P. A.
Smyth, Mark J.
Degli-Esposti, Mariapia A.
Hill, Geoffrey R.
Title GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
0006-4971
Publication date 2017-02-01
Sub-type Article (original research)
DOI 10.1182/blood-2016-08-734020
Open Access Status Not yet assessed
Volume 129
Issue 5
Start page 630
End page 642
Total pages 13
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2018
Language eng
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Medicine Publications
 
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