Expression of type 1 (interferon gamma) and type 2 (interleukin-13, interleukin-5) cytokines at distinct stages of natural killer cell differentiation from progenitor cells

被引:95
作者
Loza, MJ [1 ]
Zamai, L [1 ]
Azzoni, L [1 ]
Rosati, E [1 ]
Perussia, B [1 ]
机构
[1] Jefferson Med Coll, Kimmel Canc Ctr, Philadelphia, PA 19107 USA
关键词
D O I
10.1182/blood.V99.4.1273
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To determine whether production of type 1 and type 2 cytokines defines discrete stages of natural killer (NK) cell differentiation, cytokine expression was analyzed in human NK cells generated in vitro in the presence of interleukin-15 (IL-15) and/or IL-2 from umbilical cord blood hematopoietic progenitors. Like peripheral NK cells, the CD161(+)/CD56(+) NK cells from these cultures contained a tumor necrosis factor alpha (TNF-alpha)(+)/granulocyte macrophage-colony-stimulating factor (GM-CSF)(+) subset, an interferon gamma (IFN-gamma)(+) subset, mostly included within the former, and very few IFN-gamma(-)/IL-13(+) cells. Instead, most immature CD161(+)/CD56(-) NK cells, detectable only in the cultures with IL-2, produced IL-13, TNF-alpha, and GM-CSF, but not IFN-gamma, and contained an IL-5(+) subset. In short-term cultures with IL-12 and feeder cells, a proportion of the immature cells acquired the ability to produce IFN-gamma. Part of these produced both IFN-gamma and IL-13, irrespective of induced CD56 expression. These in vitro data indicate that ability to produce the type 2 cytokines IL-13 and IL-5 defines CD161(+) NK cells at intermediate stages of differentiation, and is lost upon terminal functional differentiation, concomitant with acquired ability to produce IFN-gamma. (C) 2002 by The American Society of Hematology.
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页码:1273 / 1281
页数:9
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