Vinante Fabrizio, Rigo Antonella, Scupoli Maria Teresa, Pizzolo Giovanni
Department of Clinical and Experimental Medicine, Section of Hematology, University of Verona, Italy.
Blood. 2002 Jan 1;99(1):52-60. doi: 10.1182/blood.v99.1.52.
The tumor necrosis factor receptor family molecule CD30 is expressed by activated and memory T cells, depending on IL-4 stimulation preferentially in association with Th0- and Th2-type responses. It mediates pleiotropic effects primarily of the inhibitory type. Arguing that CD30(+) cells have a peculiar redistribution in disease, it is demonstrated here, in the Hodgkin-derived L540 cell line (an established model for studying CD30 signaling), that CD30 regulates the prototypic lymphoid chemokine receptor CXCR4 (CD184), which plays an important role in many organ systems and is a coreceptor for human immunodeficiency virus-1 entry. CD30 stimulation with agonistic antibodies in L540 cells led to the accumulation of CXCR4 mRNA, which reached a plateau after 4 hours and did not require protein synthesis. It has been reported recently that CD30 up-regulates the transcription of CCR7 mRNA in YT lymphoma cells. After mRNA transcription, membrane expression of CXCR4 in L540 cells increased as early as 12 hours, reached a plateau after 24 hours (MFI +/- SD, 839 +/- 122 vs basal 168 +/- 28; P <.01) and was still increased after 5 days, permitting enhanced sensitivity to the chemotactic activity of CXCR4-ligand CXCL12 (CI +/- SD, 10 +/- 1 vs basal 5 +/- 2; P <.01). CD30 cross-linking also induced the release of CCL5 and CCL3 and the up-regulation of membrane binding capacity for CCL3 and CCL4 and decreased proliferative activity. This new regulatory role of CD30 may be relevant for T-cell maturation and effector responses and for promoting cancer biology.
肿瘤坏死因子受体家族分子CD30由活化的记忆T细胞表达，优先依赖白细胞介素-4刺激，与Th0型和Th2型反应相关。它主要介导抑制型的多效性作用。鉴于CD30(+)细胞在疾病中具有特殊的重新分布，本文在霍奇金来源的L540细胞系（一种用于研究CD30信号传导的成熟模型）中证明，CD30调节典型的淋巴细胞趋化因子受体CXCR4（CD184），CXCR4在许多器官系统中起重要作用，并且是人类免疫缺陷病毒-1进入的共受体。用激动性抗体刺激L540细胞中的CD30导致CXCR4 mRNA积累，4小时后达到平台期，且不需要蛋白质合成。最近有报道称，CD30上调YT淋巴瘤细胞中CCR7 mRNA的转录。mRNA转录后，L540细胞中CXCR4的膜表达最早在12小时增加，24小时后达到平台期（平均荧光强度±标准差，839±122 vs基础值168±28；P<.01），5天后仍增加，从而增强了对CXCR4配体CXCL12趋化活性的敏感性（趋化指数±标准差，10±1 vs基础值5±2；P<.01）。CD30交联还诱导CCL5和CCL3的释放以及CCL3和CCL4膜结合能力的上调，并降低增殖活性。CD30的这种新调节作用可能与T细胞成熟和效应反应以及促进癌症生物学有关。
