Interleukin-15 enhances cytotoxicity, receptor expression, and expansion of neonatal natural killer cells in long-term culture
Interleukin-15 enhances cytotoxicity, receptor expression, and expansion of neonatal natural killer cells in long-term culture
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DOI：
10.1128/cdli.11.5.879-888.2004
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发表时间：
2004-09-01
期刊：
影响因子：
--
通讯作者：
Roberts, RL
中科院分区：
文献类型：
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作者：
Choi, SS;Chhabra, VS;Roberts, RL
新生儿由于其宿主防御系统的发育缺陷，包括缺乏自然杀伤（NK）细胞功能，对各种病原体具有更高的易感性。在这项研究中，白细胞介素-15（IL-15）对新生儿NK细胞的影响进行了长达12周的培养检查。通过K562细胞杀伤测定的新鲜新生儿单核细胞（MNC）的细胞毒性最初远低于成人MNC的细胞毒性，但在用IL-15培养2周后增加超过8倍，达到与成人细胞相当的水平。这种高水平的细胞毒性可维持长达12周。在抗体依赖性细胞毒性（ADCC）试验中，使用涂有人类免疫缺陷病毒gp 120抗原的CEM细胞，IL-15大大增加了ADCC裂解MNC从脐带血。IL-15孵育5周后可使脐带MNC的CD 16（+）CD 56（+）NK标志物的表达增加5倍。用IL-15培养新生儿MNC长达10周，产生了独特的CD 3（-）CD 8（+）CD 56（+）细胞群（超过60%），这在新鲜脐带MNC中不存在。这些结果表明，IL-15可以刺激新生儿NK细胞并维持其功能数周，这对IL-15的临床应用具有意义。
Newborn infants have a higher susceptibility to various pathogens due to developmental defects in their host defense system, including deficient natural killer (NK) cell function. In this study, the effects of interleukin-15 (IL-15) on neonatal NK cells was examined for up to 12 weeks in culture. The cytotoxicity of fresh neonatal mononuclear cells (MNC) as assayed by K562 cell killing is initially much less than that of adult MNC but increases more than eightfold after 2 weeks of culture with IL-15 to a level equivalent to that of adult cells. This high level of cytotoxicity was maintained for up to 12 weeks. In antibody-dependent cellular cytotoxicity (ADCC) assays using CEM cells coated with human immunodeficiency virus gp120 antigen, IL-15 greatly increased ADCC lysis by MNC from cord blood. IL-15 increased expression of the CD16(+) CD56(+) NK markers of cord MNC fivefold after 5 weeks of incubation. Cultures of neonatal MNC with IL-15 for up to 10 weeks resulted in a unique population of CD3(-) CD8(+) CD56(+) cells (more than 60%), which are not present in fresh cord MNC. These results show that IL-15 can stimulate neonatal NK cells and sustain their function for several weeks, which has implications for the clinical use of IL-15.