CD2 promotes human natural killer cell membrane nanotube formation.

CD2 promotes human natural killer cell membrane nanotube formation.
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DOI:
10.1371/journal.pone.0047664
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Orange JS
Orange JS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Comerci CJ;Mace EM;Banerjee PP;Orange JS

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膜纳米管是物理连接两个细胞的薄膜突起。虽然纳米管已经在人类自然杀伤(NK)细胞中进行了研究,并参与帮助NK细胞的细胞毒性功能,但它们形成易感靶细胞的要求仍然不完全清楚。在这里,我们证明了CD 2-CD 58/48受体-配体相互作用促进了人NK细胞中纳米管的形成,并且是纳米管形成所必需的。在CD 2 − NK细胞系YTS中,稳定的CD 2表达变体使有效的纳米管形成成为可能,并与更好的细胞毒性功能相关。重要的是,只有NK细胞和易感靶细胞之间的相互作用与多个纳米管相关,纳米管的数量与它们的长度呈负相关。CD 2纳米管的定量活细胞荧光显微镜显示CD 2在纳米管尖端的时间依赖性富集和定位,并且阻断CD 2受体-配体相互作用防止纳米管形成。增加的纳米管形成不仅仅是受体-配体配对的特征,因为在同一细胞系系统中的KIR-MHC相互作用未能促进纳米管形成。此外,阻断LFA-1-ICAM和2B 4-CD 48受体-配体相互作用未能抑制纳米管形成。因此,只有特定的受体-配体对才能促进纳米管。CD 2还促进了离体NK细胞中纳米管的形成,这表明CD 2在NK细胞与其靶标之间纳米管的生成中起着至关重要的作用。
Membrane nanotubes are thin membranous projections that physically connect two cells. While nanotubes have been studied in human natural killer (NK) cells and are implicated in aiding NK cell cytotoxic function, requirements for their formation to susceptible target cells remain incompletely understood. Here we demonstrate that the CD2-CD58/48 receptor-ligand interaction promotes and is required for nanotube formation in human NK cells. In the CD2− NK cell line YTS, a stable CD2 expression variant enabled effective nanotube formation, and was associated with better cytotoxic function. Importantly, only interactions between an NK cell and a susceptible target cell were associated with multiple nanotubes and the number of nanotubes was inversely correlated with their length. Quantitative live cell fluorescence microscopy of CD2 nanotubes revealed time-dependent enrichment and localization of CD2 to the nanotube tip, and blocking CD2 receptor-ligand interactions prevented nanotube formation. Increased nanotube formation was not simply a feature of receptor-ligand pairing, as a KIR-MHC interaction in the same cell line system failed to promote nanotube formation. Additionally, blocking LFA-1-ICAM and 2B4-CD48 receptor-ligand interactions failed to inhibit nanotube formation. Thus only specific receptor-ligand pairs promote nanotubes. CD2 also promoted nanotube formation in ex vivo NK cells suggesting that CD2 plays a crucial role in the generation of nanotubes between an NK cell and its target.
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