The small subset of CD56bright CD16- natural killer cells is selectively responsible for both cell proliferation and interferon-γ production upon interaction with dendritic cells

The small subset of CD56bright CD16- natural killer cells is selectively responsible for both cell proliferation and interferon-γ production upon interaction with dendritic cells
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DOI:
10.1002/eji.200425100
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发表时间:
2004-06-01
影响因子:
5.4
通讯作者:
Moretta, A
Moretta, A
中科院分区:
医学3区
文献类型:
--
作者:
Vitale, M;Della Chiesa, M;Moretta, A

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NK细胞与经历成熟的树突状细胞(DC)的相遇可导致NK细胞增殖的诱导。这种增殖是否涉及大多数NK细胞或只是一个子集尚未确定。在本研究中,我们结合羧基荧光素琥珀酰亚胺酯染色和双荧光细胞荧光分析等增殖NK细胞的性质进行了分析。新鲜分离的外周血NK细胞与LIPS和未成熟的DC培养进行增殖,但是,增殖细胞仅限于一个小的NK细胞亚群。该亚群的特征为CD 56(亮)CD 16(-)NKG 2A(+)KIR(-)表面表型(KIR,杀伤Ig样受体)。细胞分选后,只有CD 56(亮)NK细胞能够响应DC刺激而增殖,而CD 56(暗)NK细胞则不能。我们还提供了证据表明,CD 56亮亚群是与DC相互作用后产生IFN-γ的NK细胞的主要来源。CD 56(亮)CD 16(-)NK细胞表达一组表面分子,包括CD 62 L、CCR 7和CXCR 3,这些分子可以使它们归巢到次级淋巴区室或炎症组织。这意味着,在体内,正在成熟的DC和CD 56(亮)NK细胞之间的相互作用可能发生在不同的组织中,并具有不同的功能意义。
The encounter of NK cells with dendritic cells (DC) undergoing maturation may result in the induction of NK cell proliferation. Whether such proliferation involves most NK cells or just a subset has yet to be determined. In the present study we analyzed the nature of such proliferating NK cells by combining carboxyfluorescein succinimidyl ester staining and double-fluorescence cytofluorimetric analysis. Freshly isolated peripheral blood NK cells cultured with LIPS and immature DC underwent proliferation;, however, proliferating cells were confined to a minor NK cell subset. This subset is characterized by the CD56(bright)CD16(-)NKG2A(+)KIR(-) surface phenotype (KIR, killer Ig-like receptor). This was further confirmed by the fact that, after cell sorting, only the CD56(bright) NK cells were able to proliferate in response to the DC stimulus, whereas the CD56 dull were not. We also provide evidence that the CD56 bright subset is the main source of IFN-gamma-producing NK cells, upon interaction with DC. The CD56(bright)CD16(-) NK cells express a panel of surface molecules including CD62L, CCR7 and CXCR3 that may allow their homing either to secondary lymphoid compartments or to inflamed tissues. This implies that, in vivo, the interactions between DC undergoing maturation and CD56(bright) NK cells may occur,in different tissues and have different functional implications.