Natural killer-cell differentiation by myeloid progenitors

作者：Grzywacz Bartosz; Kataria Nandini; Kataria Niketa; Blazar Bruce R; Miller Jeffrey S; Verneris Michael R^*

来源：Blood, 2011, 117(13): 3548-3558.

DOI：10.1182/blood-2010-04-281394

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 CD56dim subset of NK cells. Collectively, these studies show that NK cells can be derived from the myeloid lineage. (Blood. 2011;117(13):3548-3558)

• 出版日期2011-3-31