Naume B, Gately M K, Desai B B, Sundan A, Espevik T
Institute of Cancer Research, University of Trondheim, Norway.
Cytokine. 1993 Jan;5(1):38-46. doi: 10.1016/1043-4666(93)90022-w.
Our previous studies have demonstrated that interleukin12 (IL-12) (cytotoxic lymphocyte maturation factor/NK cell stimulatory factor) and IL-7 alone have the ability to generate high LAK activity and low proliferative activity in CD56+ NK cells. This study was undertaken to examine the influence of IL-4 on the IL-12-induced activation of CD56+ NK cells. IL-4 did not affect the IL-12-induced generation of LAK activity in CD56+ cells, in contrast to an inhibition of IL-2 and IL-7-induced LAK activity. Most interestingly, the combination of IL-4 and IL-12 resulted in a synergistic proliferative activity (8-fold) in the CD56+ NK cells, and a marked increase in the cell yield at day 5 was detected. Furthermore, the potent effect of IL-4 on IL-12-induced proliferation was restricted to the CD56+ NK cells, as CD56- cell populations were found unresponsive to the combination of IL-4 and IL-12. Furthermore, IL-4 induced a slight increase in the IL-12-stimulated TNF production. IL-12 enhanced the IL-12 receptor (R) expression and IL-4R expression in the CD56+ NK cells. Combined treatment with IL-12 and IL-4 further enhanced the IL-12R expression, most prominently in the CD56+, CD16- NK subpopulation. The increased IL-4R expression induced by IL-12 and the increased IL-12R expression induced by IL-4 may explain the synergistic proliferative activity detected in response to IL-12 and IL-4. IL-4 seems to possess unique stimulatory properties towards resting CD56+ NK cells, when used as a costimulus with IL-12.
我们之前的研究表明，白细胞介素12（IL-12）（细胞毒性淋巴细胞成熟因子/自然杀伤细胞刺激因子）和单独的IL-7能够在CD56+自然杀伤细胞中产生高活性的淋巴因子激活的杀伤细胞（LAK）活性和低增殖活性。本研究旨在检测IL-4对IL-12诱导的CD56+自然杀伤细胞激活的影响。与抑制IL-2和IL-7诱导的LAK活性相反，IL-4不影响IL-12诱导的CD56+细胞中LAK活性的产生。最有趣的是，IL-4和IL-12的组合在CD56+自然杀伤细胞中产生了协同增殖活性（8倍），并且在第5天检测到细胞产量显著增加。此外，IL-4对IL-12诱导的增殖的强效作用仅限于CD56+自然杀伤细胞，因为发现CD56-细胞群体对IL-4和IL-12的组合无反应。此外，IL-4诱导IL-12刺激的肿瘤坏死因子（TNF）产生略有增加。IL-12增强了CD56+自然杀伤细胞中IL-12受体（R）的表达和IL-4受体的表达。IL-12和IL-4联合处理进一步增强了IL-12R的表达，最显著的是在CD56+、CD16-自然杀伤细胞亚群中。IL-12诱导的IL-4受体表达增加和IL-4诱导的IL-12受体表达增加可能解释了对IL-12和IL-4反应中检测到的协同增殖活性。当与IL-12作为共刺激因子使用时，IL-4似乎对静止的CD56+自然杀伤细胞具有独特的刺激特性。
