| First Author | Bunting MD | Year | 2017 |
| Journal | Blood | Volume | 129 |
| Issue | 5 | Pages | 630-642 |
| PubMed ID | 27927647 | Mgi Jnum | J:239957 |
| Mgi Id | MGI:5882134 | Doi | 10.1182/blood-2016-08-734020 |
| Citation | Bunting MD, et al. (2017) GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity. Blood 129(5):630-642 |
| abstractText | 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-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. |
