Regulation of human NK-cell cytokine and chemokine production by target cell recognition
Regulation of human NK-cell cytokine and chemokine production by target cell recognition
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DOI：
10.1182/blood-2009-08-238469
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发表时间：
2010-03-18
期刊：
影响因子：
20.3
通讯作者：
Bryceson, Yenan T.
中科院分区：
文献类型：
--
作者：
Fauriat, Cyril;Long, Eric O.;Bryceson, Yenan T.
自然杀伤 (NK) 细胞对感染细胞或肿瘤细胞的识别可诱导细胞毒性和细胞因子分泌。到目前为止，很难评估多种 NK 细胞激活受体对靶细胞识别后细胞因子和趋化因子产生的相对贡献。使用表达 NK 细胞受体 LFA-1、NKG2D、DNAM-1、2B4 和 CD16 配体的果蝇细胞，我们研究了新鲜分离的人类 NK 细胞分泌的最低要求。靶细胞刺激主要诱导促炎细胞因子和趋化因子的分泌。刺激后 1 小时内诱导趋化因子 MIP-1 α、MIP-1 β 和 RANTES 的释放，而 TNF-α 和 IFN-γ 的释放发生较晚。 CD16、2B4 或 NKG2D 的参与足以释放趋化因子，而 TNF-α 和 IFN-γ 的诱导需要其他受体的参与。值得注意的是，我们的结果表明，在识别靶细胞后，CD56(dim) NK 细胞比 CD56(bright) NK 细胞更能产生细胞因子和趋化因子。目前的数据证明了特定靶细胞配体如何决定 NK 细胞细胞因子和趋化因子反应的定性和时间方面。从概念上讲，结果表明 CD56(dim) NK 细胞在识别异常细胞时是细胞因子和趋化因子的重要来源，根据所参与的激活受体的多样性产生分级反应。 （血。2010；115：2167-2176）
Natural killer (NK)-cell recognition of infected or neoplastic cells can induce cytotoxicity and cytokine secretion. So far, it has been difficult to assess the relative contribution of multiple NK-cell activation receptors to cytokine and chemokine production upon target cell recognition. Using Drosophila cells expressing ligands for the NK-cell receptors LFA-1, NKG2D, DNAM-1, 2B4, and CD16, we studied the minimal requirements for secretion by freshly isolated, human NK cells. Target cell stimulation induced secretion of predominately proinflammatory cytokines and chemokines. Release of chemokines MIP-1 alpha, MIP-1 beta, and RANTES was induced within 1 hour of stimulation, whereas release of TNF-alpha and IFN-gamma occurred later. Engagement of CD16, 2B4, or NKG2D sufficed for chemokine release, whereas induction of TNF-alpha and IFN-gamma required engagement of additional receptors. Remarkably, our results revealed that, upon target cell recognition, CD56(dim) NK cells were more prominent cytokine and chemokine producers than CD56(bright) NK cells. The present data demonstrate how specific target cell ligands dictate qualitative and temporal aspects of NK-cell cytokine and chemokine responses. Conceptually, the results point to CD56(dim) NK cells as an important source of cytokines and chemokines upon recognition of aberrant cells, producing graded responses depending on the multiplicity of activating receptors engaged. (Blood. 2010;115:2167-2176)