title: Natural killer-cell differentiation by myeloid progenitors.
abstract: Because lymphoid progenitors can give rise to natural killer (NK) cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that rare human CD34(+) hematopoietic progenitors develop into NK cells in vitro in the presence of cytokines (interleukin-7, interleukin-15, stem cell factor, and fms-like tyrosine kinase-3 ligand). Adding hydrocortisone and stromal cells greatly increases the frequency of progenitor cells that give rise to NK cells through the recruitment of myeloid precursors, including common myeloid progenitors and granulocytic-monocytic precursors to the NK-cell lineage. WNT signaling was involved in this effect. Cells at more advanced stages of myeloid differentiation (with increasing expression of CD13 and macrophage colony-stimulating factor receptor [M-CSFR]) could also differentiate into NK cells in the presence of cytokines, stroma, and hydrocortisone. NK cells derived from myeloid precursors (CD56(-)CD117(+)M-CSFR(+)) showed more expression of killer immunoglobulin-like receptors, a fraction of killer immunoglobulin-like receptor-positive-expressing cells that lacked NKG2A, a higher cytotoxicity compared with CD56(-)CD117(+)M-CSFR(-) precursor-derived NK cells and thus resemble the CD56(dim) subset of NK cells. Collectively, these studies show that NK cells can be derived from the myeloid lineage.
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, 425 E. River Road, Minneapolis, MN 55455, USA.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Grzywacz
authors.forename: Nandini
authors.initials: N
authors.lastname: Kataria
authors.forename: Niketa
authors.initials: N
authors.lastname: Kataria
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D019002:CD56 Antigen; C522918:NCAM1 protein, human; D006854:Hydrocortisone