GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity
Details
Publication Year 2017-12-07, Volume 129, Issue #5, Page 630-642
Journal Title
Blood
Publication Type
Journal Article
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 IL-15, and administration of IL-15/IL-15Ralpha 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.
Publisher
ASH
WEHI Research Division(s)
Molecular Immunology
PubMed ID
27927647
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-05-26 03:11:42
Last Modified: 2017-05-26 03:16:25
An error has occurred. This application may no longer respond until reloaded. Reload 🗙