Biron C A, Nguyen K B, Pien G C, Cousens L P, Salazar-Mather T P
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA.
Annu Rev Immunol. 1999;17:189-220. doi: 10.1146/annurev.immunol.17.1.189.
Natural killer (NK) cells are populations of lymphocytes that can be activated to mediate significant levels of cytotoxic activity and produce high levels of certain cytokines and chemokines. NK cells respond to and are important in defense against a number of different infectious agents. The first indications for this function came from the observations that virus-induced interferons alpha/beta (IFN-alpha and -beta) are potent inducers of NK cell-mediated cytotoxicity, and that NK cells are important contributors to innate defense against viral infections. In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production. Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms. However, high levels of IFN-alpha/beta appear to be unique and/or uniquely dominant in the context of viral infections and act to regulate other innate responses, including induction of NK cell proliferation in vivo and overall negative regulation of IL-12 production. A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.
自然杀伤（NK）细胞是一类淋巴细胞群体，可被激活以介导显著水平的细胞毒性活性，并产生高水平的某些细胞因子和趋化因子。NK细胞对多种不同的感染因子做出反应，并在抵御这些感染因子中发挥重要作用。这一功能的最初迹象来自于以下观察结果：病毒诱导的α/β干扰素（IFN-α和-β）是NK细胞介导的细胞毒性的强效诱导剂，并且NK细胞是先天性抗病毒防御的重要贡献者。除了IFN-α/β之外，多种其他先天性细胞因子也可以介导调节NK细胞细胞毒性、增殖和γ干扰素（IFN-γ）产生反应的生物学功能。某些（但不是所有）病毒感染会诱导白细胞介素12（IL-12），从而引发NK细胞产生IFN-γ并启动抗病毒机制。然而，高水平的IFN-α/β在病毒感染的背景下似乎是独特的和/或具有独特的主导作用，并且可调节其他先天性反应，包括体内NK细胞增殖的诱导以及IL-12产生的整体负调节。一幅关于特定先天性细胞因子激活NK细胞反应及其在提供独特内环境以促进下游适应性反应（这在抵御病毒感染中最为有益）方面的协同作用的详细图景正在形成。
