Natural killler (NK) cells share a progenitor with T cells (Douagi et al. 2002; Ikawa et al. 1999; Raulet 2003; Rothenberg et al. 2003) but do not require the thymic microenvironment for maturation. Instead, strontium 89 and other agents that disrupt the bone marrow have been shown in mice to impair NK cell development (Kumar et al. 1979; Seaman et al. 1979). Moreover, a cytokine produced by bone marrow stromal cells, IL-15, plays a central role in NK cell development and survival (Kennedy et al. 2000; Lodolce et al. 1998). Administration of another factor produced by stromal cells, Flt3L, has been shown to cause expansion of NK cells (Brasel et al. 1996; Shaw et al. 1998). Very little is known about NK cell ontogeny in humans (Raulet 2003); however, Toivanen et al. (1981) reported that the development of functional NK cells in the human fetus occurs at 28 weeks of gestation. Moreover, levels of NK cells have been demonstrated to be significantly higher during fetal life than during the neonatal period, perhaps indicating a more important role for NK cells in fetal development than in adaptive immunity (West 2002).
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