Hematopoietic origin of human natural killer (NK) cells: generation from immature progenitors

Human natural killer (NK) cells originate from bone marrow, but little is known about NK cell progenitors and ontogeny. We studied the phenotype and functional activity of NK cells derived from highly purified human bone marrow CD34+ cells, which exhibited neither lytic activity nor expression of surface antigens characteristic of NK (CD56) or T (CD3) cells. However, when cultured with hematopoietic growth factors or feeder layers for up to 4 weeks, up to 86% functional CD56+ cells were seen in the absence of mature T cell development. CD56+ cells appeared in all cultures at 2 or 3 weeks, with the largest percentage in those exposed to IL-2. These studies demonstrated that NK cells arise 'in vitro' from immature bone marrow progenitors and also suggest a separate origin and differentiation pathway for NK and T cells.