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dc.contributor.authorHuntington, ND
dc.contributor.authorLegrand, N
dc.contributor.authorAlves, NL
dc.contributor.authorJaron, B
dc.contributor.authorWeijer, K
dc.contributor.authorPlet, A
dc.contributor.authorCorcuff, E
dc.contributor.authorMortier, E
dc.contributor.authorJacques, Y
dc.contributor.authorSpits, H
dc.contributor.authorDi Santo, JP
dc.date.accessioned2021-02-05T00:54:31Z
dc.date.available2021-02-05T00:54:31Z
dc.date.issued2009-01-16
dc.identifierpii: jem.20082013
dc.identifier.citationHuntington, N. D., Legrand, N., Alves, N. L., Jaron, B., Weijer, K., Plet, A., Corcuff, E., Mortier, E., Jacques, Y., Spits, H. & Di Santo, J. P. (2009). IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. JOURNAL OF EXPERIMENTAL MEDICINE, 206 (1), pp.25-34. https://doi.org/10.1084/jem.20082013.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/260201
dc.description.abstractThe in vivo requirements for human natural killer (NK) cell development and differentiation into cytotoxic effectors expressing inhibitory receptors for self-major histocompatibility complex class I (MHC-I; killer Ig-like receptors [KIRs]) remain undefined. Here, we dissect the role of interleukin (IL)-15 in human NK cell development using Rag2(-/-)gamma c(-/-) mice transplanted with human hematopoietic stem cells. Human NK cell reconstitution was intrinsically low in this model because of the poor reactivity to mouse IL-15. Although exogenous human IL-15 (hIL-15) alone made little improvement, IL-15 coupled to IL-15 receptor alpha (IL-15R alpha) significantly augmented human NK cells. IL-15-IL-15R alpha complexes induced extensive NK cell proliferation and differentiation, resulting in accumulation of CD16(+)KIR(+) NK cells, which was not uniquely dependent on enhanced survival or preferential responsiveness of this subset to IL-15. Human NK cell differentiation in vivo required hIL-15 and progressed in a linear fashion from CD56(hi)CD16(-)KIR(-) to CD56(lo)CD16(+)KIR(-), and finally to CD56(lo)CD16(+)KIR(+). These data provide the first evidence that IL-15 trans-presentation regulates human NK cell homeostasis. Use of hIL-15 receptor agonists generates a robust humanized immune system model to study human NK cells in vivo. IL-15 receptor agonists may provide therapeutic tools to improve NK cell reconstitution after bone marrow transplants, enhance graft versus leukemia effects, and increase the pool of IL-15-responsive cells during immunotherapy strategies.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleIL-15 trans-presentation promotes human NK cell development and differentiation in vivo
dc.typeJournal Article
dc.identifier.doi10.1084/jem.20082013
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume206
melbourne.source.issue1
melbourne.source.pages25-34
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1040314
melbourne.contributor.authorHuntington, Nicholas
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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