Chin T W, Plaeger-Marshall S, Ank B J, Pressman S R, Stiehm E R
Department of Pediatrics, University of California, Los Angeles School of Medicine.
Nat Immun Cell Growth Regul. 1991;10(5):237-46.
Deficient cellular cytotoxic mechanisms are present in neonates, contributing to their increased susceptibility to certain viruses, notably herpes simplex virus (HSV). Significant lymphokine-activated killer (LAK) cell activity has been described in cord blood, suggesting a possible role for LAK and/or interleukin-2 (IL-2) therapy in newborns with serious viral infections. The effect of HSV (type 1) on the activation of cord versus adult LAK cells was investigated by adding virus (multiplicity of infection, MOI = 10) to cells that had been previously incubated for 4-6 days with IL-2 (50-100 U/ml). The cells were then tested 24 h after virus exposure for cytotoxic activity against 51Cr-labelled K562 and Raji target cells. HSV inhibited LAK cytotoxicity of adult cells against K562 by 44% (72 +/- 2.4%, SEM; specific lysis to 40 +/- 6.2%, n = 15) and by 62% against Raji targets (50 +/- 5.6 to 19 +/- 4.4%). A similar degree of inhibition was observed for cord cells against K562 (76 +/- 2.0 to 46 +/- 5.3%) and Raji (60 +/- 4.6 to 24 +/- 6.2%). The degree of inhibition was correlated with the dose of virus in dose-response experiments. Inhibition was also noted with irradiated (10,000 rad) but not with heat-inactivated (56 degrees C for 60 min) virus. No inhibition was found when virus was added directly to the cytotoxic assay or when virus was added at the initiation or end of culture of cells with IL-2 (i.e. day 0 or day 5-7). In contrast, HSV stimulated cytotoxic activity against both the natural killer (NK)-sensitive (K562) and NK-resistant (Raji) targets in cells not incubated with IL-2. The cytotoxicity of adult cells incubated with infectious HSV (MOI = 10) for 5-7 days increased from 5.5 +/- 1.9% in the absence of virus to 25 +/- 6.0% against K562 in the presence of virus and from 3.5 +/- 1.0 (no virus) to 16 +/- 4.3% (with virus) against Raji targets (n = 8). The cytotoxicity of cord cells was also stimulated, but to a lesser degree. Irradiated virus also stimulated cytotoxic activity but to a lesser degree in cord cells. Virus-induced nonspecific cytotoxicity may represent an important component of the host's antiviral defense that is present at birth, but somewhat diminished compared to normal adults.
新生儿存在细胞毒性机制缺陷，这导致他们对某些病毒，尤其是单纯疱疹病毒（HSV）的易感性增加。已有研究描述了脐血中显著的淋巴因子激活的杀伤（LAK）细胞活性，提示LAK和/或白细胞介素-2（IL-2）疗法在患有严重病毒感染的新生儿中可能发挥作用。通过将病毒（感染复数，MOI = 10）添加到先前用IL-2（50 - 100 U/ml）孵育4 - 6天的细胞中，研究了HSV（1型）对脐血LAK细胞与成人LAK细胞激活的影响。然后在病毒暴露24小时后测试细胞对51Cr标记的K562和Raji靶细胞的细胞毒性活性。HSV抑制成人细胞对K562的LAK细胞毒性44%（72±2.4%，SEM；特异性裂解至40±6.2%，n = 15），对Raji靶细胞的抑制率为62%（50±5.6%至19±4.4%）。脐血细胞对K562（76±2.0%至46±5.3%）和Raji（60±4.6%至24±6.2%）的抑制程度相似。在剂量反应实验中，抑制程度与病毒剂量相关。用辐照（10,000拉德）病毒也观察到抑制作用，但热灭活（56℃60分钟）病毒则未观察到抑制作用。当病毒直接添加到细胞毒性测定中或在细胞用IL-2培养的起始或结束时（即第0天或第5 - 7天）添加病毒时，未发现抑制作用。相比之下，HSV刺激了未用IL-2孵育的细胞对自然杀伤（NK）敏感（K562）和NK抗性（Raji）靶细胞的细胞毒性活性。用感染性HSV（MOI = 10）孵育5 - 7天的成人细胞的细胞毒性从无病毒时的5.5±1.9%增加到有病毒时对K562的25±6.0%，对Raji靶细胞从3.5±1.0（无病毒）增加到16±4.3%（有病毒）（n = 8）。脐血细胞的细胞毒性也受到刺激，但程度较小。辐照病毒也刺激了细胞毒性活性，但在脐血细胞中的刺激程度较小。病毒诱导的非特异性细胞毒性可能代表宿主抗病毒防御的一个重要组成部分，这种防御在出生时就存在，但与正常成年人相比有所减弱。
