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
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
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DOI：
10.1182/blood.v99.4.1273
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发表时间：
2002-02-15
期刊：
影响因子：
20.3
通讯作者：
Perussia, B
中科院分区：
文献类型：
--
作者：
Loza, MJ;Zamai, L;Perussia, B
为了确定1型和2型细胞因子的产生是否决定了自然杀伤细胞（NK）分化的不同阶段，我们分析了体外培养的人NK细胞中白细胞介素-15 （IL-15）和/或来自脐带血造血祖细胞的IL-2的细胞因子表达。与外周NK细胞一样，来自这些培养的CD161(+)/CD56(+) NK细胞含有肿瘤坏死因子α (tnf - α)(+)/粒细胞巨噬细胞集落刺激因子（GM-CSF）（+）亚群，干扰素γ (ifn - γ)（+）亚群，主要包括在前者中，很少包括ifn - γ (-)/IL-13（+）细胞。相反，大多数未成熟的CD161(+)/CD56(-) NK细胞（仅在IL-2培养中可检测到）产生IL-13、tnf - α和GM-CSF，但不产生ifn - γ，并且含有IL-5（+）亚群。在IL-12和饲养细胞的短期培养中，一部分未成熟细胞获得了产生ifn - γ的能力。这些细胞的一部分同时产生ifn - γ和IL-13，与诱导的CD56表达无关。这些体外数据表明，产生2型细胞因子IL-13和IL-5的能力决定了CD161(+) NK细胞在分化的中间阶段，并在最终功能分化时丧失，同时获得产生ifn - γ的能力。(C) 2002年由美国血液病学会出版。
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.