Armant M, Ishihara H, Rubio M, Delespesse G, Sarfati M
University of Montreal, Notre-Dame Hospital Research Center, Quebec, Canada.
J Exp Med. 1994 Sep 1;180(3):1005-11. doi: 10.1084/jem.180.3.1005.
Soluble CD23 (sCD23) has multiple IgE-independent biological activities. In the present study, we examined the regulatory effect of sCD23 on cytokine production by human peripheral blood mononuclear cells (PBMC). We show that sCD23 enhances by about 80-fold the interleukin 2 (IL-2)-induced interferon gamma (IFN-gamma) production and by about 10-fold the response to IL-12. This potentiating activity is time and dose dependent and is not associated with a significant effect on DNA synthesis. The sCD23 costimulatory activity for IFN-gamma synthesis is drastically reduced in monocyte-depleted PBMC, suggesting that monocytes may be the target for sCD23. This hypothesis was supported by the following observations. First, sCD23 alone is a potent inducer of tumor necrosis factor alpha (TNF-alpha) production by PBMC and this effect disappears after monocyte depletion. The triggering of TNF-alpha release is specifically inhibited by neutralizing anti-CD23 monoclonal antibody (mAb). In addition, IL-2 and IL-12 synergize with sCD23 to induce TNF-alpha production. Second, sCD23 triggers the release of other inflammatory mediators such as IL-1 alpha, IL-1 beta, and IL-6. Finally, TNF-alpha production in response to IL-2 and sCD23 precedes IFN-gamma and IFN-gamma secretion is significantly inhibited by anti-TNF-alpha mAb, indicating that the sCD23 costimulatory signal for IFN-gamma production may be partially mediated by TNF-alpha release. It is proposed that sCD23 is a proinflammatory cytokine that, in addition, may play an important role in the control of the immune response via the enhancement of IFN-gamma production.
可溶性CD23（sCD23）具有多种不依赖于免疫球蛋白E（IgE）的生物学活性。在本研究中，我们检测了sCD23对人外周血单个核细胞（PBMC）细胞因子产生的调节作用。我们发现，sCD23可使白细胞介素2（IL-2）诱导的γ干扰素（IFN-γ）产生增加约80倍，并使对IL-12的反应增强约10倍。这种增强活性具有时间和剂量依赖性，且与对DNA合成无显著影响相关。在单核细胞耗竭的PBMC中，sCD23对IFN-γ合成的共刺激活性大幅降低，提示单核细胞可能是sCD23的作用靶点。以下观察结果支持了这一假说。首先，单独的sCD23是PBMC产生肿瘤坏死因子α（TNF-α）的有效诱导剂，单核细胞耗竭后这种作用消失。中和性抗CD23单克隆抗体（mAb）可特异性抑制TNF-α释放的触发。此外，IL-2和IL-12与sCD23协同诱导TNF-α产生。其次，sCD23触发其他炎症介质如IL-1α、IL-1β和IL-6的释放。最后，对IL-2和sCD23的反应中TNF-α的产生先于IFN-γ，且抗TNF-α mAb可显著抑制IFN-γ的分泌，表明sCD23对IFN-γ产生的共刺激信号可能部分由TNF-α释放介导。有人提出，sCD23是一种促炎细胞因子，此外，它可能通过增强IFN-γ产生在免疫反应的调控中发挥重要作用。
