Positive self regulation of cytotoxicity in human natural killer cells by production of interferon upon exposure to influenza and herpes viruses.
Positive self regulation of cytotoxicity in human natural killer cells by production of interferon upon exposure to influenza and herpes viruses.
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DOI：
10.1084/jem.156.4.1222
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发表时间：
1982-10-01
期刊：
影响因子：
--
通讯作者：
Herberman RB
中科院分区：
文献类型：
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作者：
Djeu JY;Stocks N;Zoon K;Stanton GJ;Timonen T;Herberman RB
A/PC 和 HSV-1 病毒自然杀伤 (NK) 活性的增强似乎是由 NK 细胞群本身诱导干扰素 (IFN) 引起的。这些病毒诱导人大颗粒淋巴细胞 (LGL) 产生高水平的干扰素，可以通过 Percoll 密度梯度从外周血中轻松分离出大颗粒淋巴细胞 (LGL)。这些 LGL 先前已被证明可解释内源性 NK 活性并与内源性 NK 活性高度相关，在 IFN 诱导的 18 小时期间其裂解功能增强。 NK-IFN 系统似乎不需要非 LGL 辅助细胞（T 细胞、B 细胞或单核细胞）。通过用 OKT3 加补体、抗 IgM 加补体处理或用二氧化硅或角叉菜胶预孵育来去除后一种细胞类型，对 LGL 响应病毒的能力没有影响。与病毒一起培养 18 小时的单核细胞也检测到 IFN 的产生，尽管水平较低，但没有诱导细胞毒性活性。另一方面，T 细胞，即使在单核细胞存在的情况下，也没有表现出这两种特性，并且更长的培养物（病毒长达 4 天）仍然没有改变这种模式。 LGL 和单核细胞产生的 IFN 主要是 IFN-α，通过使用 IFN-α、β 和 γ 抗血清的中和测定进行评估。然而，在具有可检测到的 A/PC 流感血清抗体的个体中，LGL 中诱导的 IFN 似乎是 γ 型，可能是因为病毒的特异性识别。这些数据表明 NK 细胞中存在有效的积极自我调节机制，可以很容易地被病毒开启。
Augmentation of natural killer (NK) activity by influenza A/PC and HSV- 1 viruses appears to be caused by the induction of interferon (IFN) within the NK cell population itself. These viruses induced high levels of IFN production by human large granular lymphocytes (LGL) that could be readily isolated from peripheral blood by Percoll density gradients. These LGL, which have been previously shown to account for and to be highly associated with endogenous NK activity, became augmented in their lytic function during the 18-h period that IFN was induced. Non- LGL helper cells did not appear to be required in the NK-IFN system (either T cells, B cells, or monocytes). Removal of these latter cell types by treatment with OKT3 plus complement, anti-IgM plus complement, or preincubation with silica or carrageenan had no effect on the ability of LGL to respond to the viruses. Production of IFN was also detected, albeit at lower levels, from monocytes cultured for 18 h with viruses, but no cytotoxic activity was induced. On the other hand, T cells, even in the presence of monocytes, showed neither property, and longer cultures, with virus up to 4 d, still did not alter the pattern. The IFN produced by both LGL and monocytes were predominantly IFN- alpha, as assessed by neutralization assays with antisera to IFN-alpha, -beta, and -gamma. In an individual with detectable serum antibodies to influenza A/PC, however, the IFN induced in LGL appeared to be gamma, presumably because of specific recognition of the virus. These data suggest an efficient positive self-regulatory mechanism in NK cells that may be readily switched on by viruses.