Immune modulation of natural killer cell cytotoxicity against herpes infected target cells in pregnancy.
Immune modulation of natural killer cell cytotoxicity against herpes infected target cells in pregnancy.
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自然杀伤细胞对妊娠期疱疹感染靶细胞的细胞毒性的免疫调节。
DOI：
10.1111/j.1600-0897.1990.tb01045.x
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Crump,J
中科院分区：
文献类型：
--
作者：
Gonik,B;Loftin,KC;Tan,NS;Crump,J
自然杀伤细胞的细胞毒性（NKC）是一种非特异性的，主要的免疫防御系统，对各种病原体，包括单纯疱疹病毒（HSV）。有证据表明，在怀孕期间，NKC减弱。这种免疫衰减的调节机制尚未确定。我们利用HSV感染的靶细胞模型，检查了两种细胞因子（白细胞介素-2 [IL-2]和α干扰素[IFN]）在妊娠期间改变NKC反应性的能力。通过Ficoll-Paque分离法从19例妊娠和19例非妊娠受试者中分离外周单核效应细胞。将这些细胞与IFN、IL-2或单独培养基一起孵育，并通过18 h铬释放试验分析%NKC。与非妊娠对照相比，使用来自妊娠受试者的效应细胞的NKC百分比较低。与IFN或IL-2孵育导致妊娠和非妊娠衍生细胞中NKC显著增加。妊娠和非妊娠来源细胞之间的IL-2剂量要求或达到的细胞毒性水平（分别为43.1 ± 6.8%和44.4 ± 6.8%）无差异。在妊娠期，IFN介导的NKC增强作用在达到的细胞毒性绝对水平（分别为26.1 ± 3.9%和37.2 ± 4.9%）和生成的剂量反应曲线方面均有所减弱。这些结果表明，抗HSV感染细胞的NKC在妊娠期间减弱，并且可以使用IFN和IL-2进行免疫调节。然而，在妊娠期间，IFN对NKC反应性的恢复仍然不完全，这表明这种细胞因子的作用机制与IL-2不同。
Natural killer cell cytotoxicity (NKC) is a nonspecific, primary immunodefense system active against a variety of pathogens, including herpes simplex virus (HSV). Evidence suggests that during pregnancy, NKC is attenuated. The regulatory mechanisms for this immune attenuation have yet to be defined. We examined two cytokines (interleukin‐2 [IL‐2] and alpha interferon [IFN]) for their ability to alter NKC responsiveness during pregnancy, utilizing an HSV‐infected target cell model. Peripheral mononuclear effector cells were isolated from 19 pregnant and 19 nonpregnant subjects by Ficoll‐Paque separation. These cells were incubated with IFN, IL‐2, or media alone, and analyzed for %NKC by an 18 h chromium release assay. The percentage of NKC was lower using the effector cells from the pregnant subjects as compared to nonpregnant controls. Incubation with either IFN or IL‐2 resulted in a significant augmentation of NKC in both the pregnant and nonpregnant derived cells. There were no differences in IL‐2 dose requirements or levels of cytotoxicity achieved (43.1 ± 6.8% vs. 44.4 ± 6.8%, respectively) between pregnant and nonpregnant derived cells. The IFN‐mediated augmentation of NKC was somewhat blunted in pregnancy both in terms of absolute levels of cytotoxicity achieved (26.1 ± 3.9% vs. 37.2 ± 4.9%, respectively) and dose response curves generated. These results demonstrate that NKC against HSV infected cells is attenuated during pregnancy and can be immunoregulated with the use of either IFN and IL‐2. The restoration of NKC responsiveness with IFN, however, remains incomplete during pregnancy, suggesting that this cytokine's mechanism of action differs from that of IL‐2.