CCL16/LEC powerfully triggers effector and antigen-presenting functions of macrophages and enhances T cell cytotoxicity
CCL16/LEC powerfully triggers effector and antigen-presenting functions of macrophages and enhances T cell cytotoxicity
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DOI：
10.1189/jlb.0403146
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发表时间：
2004-01-01
影响因子：
5.5
通讯作者：
Giovarelli, M
中科院分区：
文献类型：
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作者：
Cappello, P;Caorsi, C;Giovarelli, M
人CC趋化因子CCL16是一种肝脏表达的趋化因子，通过触发肿瘤坏死因子α (tnf - α)和Fas配体的表达来增强小鼠腹腔巨噬细胞的杀伤活性。巨噬细胞对CCL16的反应还包括增强单核细胞趋化蛋白-1的产生，正常T细胞表达和分泌趋化因子，以及白细胞介素(IL)-1 β、tnf - α和IL-12。CCL16的作用几乎与脂多糖和干扰素一样强，这两种是最好的巨噬细胞激活剂。此外，ccl16活化的巨噬细胞过表达膜CD80、CD86和CD40共刺激分子，广泛吞噬肿瘤细胞碎片。一旦暴露在这些碎片中，它们就会在原始T细胞中激活一种强烈的、肿瘤特异性的细胞溶解反应。此外，在CCL16存在下产生的细胞溶解性T细胞显示出更高的细胞毒性，并在肿瘤靶细胞中激活caspase-8。这种激活caspase-8的能力取决于CCL16诱导的tnf - α和Fas配体的过度表达。这些数据揭示了CCL16在免疫应答场景中的新功能。CCL16显著增强巨噬细胞的效应和抗原呈递功能，增强T细胞的裂解活性。
The human CC chemokine CCL16, a liver-expressed chemokine, enhances the killing activity of mouse peritoneal macrophages by triggering their expression of tumor necrosis factor alpha (TNF-alpha) and Fas ligand. Macrophages also respond to CCL16 by enhancing their production of monocyte chemoattractant protein-1, regulated on activation, normal T cells expressed and secreted chemokines, and interleukin (IL)-1beta, TNF-alpha, and IL-12. The effect of CCL16 is almost as strong as that of lipopolysaccharide and interferon-gamma, two of the best macrophage activators. Moreover, CCL16-activated macrophages overexpress membrane CD80, CD86, and CD40 costimulatory molecules and extensively phagocytose tumor cell debris. On exposure to such debris, they activate a strong, tumor-specific, cytolytic response in virgin T cells. Furthermore, cytolytic T cells generated in the presence of CCL16 display a higher cytotoxicity and activate caspase-8 in tumor target cells. This ability to activate caspase-8 depends on their overexpression of TNF-alpha and Fas ligand induced by CCL16. These data reveal a new function for CCL16 in the immune-response scenario. CCL16 significantly enhances the effector and the antigen-presenting function of macrophages and augments T cell lytic activity.