Cutting edge:: induction of IFN-γ production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells
Cutting edge:: induction of IFN-γ production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells
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DOI：
10.4049/jimmunol.167.4.1877
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发表时间：
2001-08-15
影响因子：
4.4
通讯作者：
Long, EO
中科院分区：
文献类型：
--
作者：
Rajagopalan, S;Fu, J;Long, EO
活化的NK细胞裂解肿瘤细胞和病毒感染的细胞，并在与敏感的靶细胞接触时产生IFN-γ。静息NK细胞中这些效应子应答的调节尚不清楚。我们现在描述了一种受体KIR 2DL 4，其具有在不存在细胞因子的情况下通过静息NK细胞诱导IFN-γ产生而非细胞毒性的独特性质。相反，NK细胞活化受体CD 16和2B 4诱导细胞毒性，但不产生IFN-γ。与IL-2诱导的IFN-γ分泌对细胞外信号调节激酶丝裂原活化蛋白激酶途径的抑制敏感相反，静息NK细胞通过KIR 2DL 4诱导的IFN-γ产生被p38丝裂原活化蛋白激酶信号传导途径的抑制剂阻断。这些结果揭示了在静息NK细胞的反应中的功能二分法（细胞因子产生与细胞毒性），如由个体受体的信号所指示的。
Activated NK cells lyse tumor cells and virus-infected cells and produce IFN-gamma upon contact with sensitive target cells. The regulation of these effector responses in resting NK cells is not well understood. We now describe a receptor, KIR2DL4, that has the unique property of inducing IFN-gamma production, but not cytotoxicity, by resting NK cells in the absence of cytokines. In contrast, the NK cell-activation receptors CD16 and 2B4 induced cytotoxicity but not IFN-gamma production. The induction by KIR2DL4 of IFN-gamma production by resting NK cells was blocked by an inhibitor of the p38 mitogen-activated protein kinase signaling pathway, in contrast to the IL-2-induced IFN-gamma secretion that was sensitive to inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase pathway. These results reveal a functional dichotomy (cytokine production vs cytotoxicity) in the response of resting NK cells, as dictated by the signals of individual receptors.