Induction of CD83+ CD14+ nondendritic antigen-presenting cells by exposure of monocytes to IFN-α
Induction of CD83+ CD14+ nondendritic antigen-presenting cells by exposure of monocytes to IFN-α
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DOI：
10.4049/jimmunol.181.5.2999
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Pimpinelli, Nicola
中科院分区：
文献类型：
--
作者：
Gerlini, Gianni;Mariotti, Giulia;Pimpinelli, Nicola
IFN-α是用于治疗病毒性和恶性疾病的众所周知的药剂。它有几种作用模式，包括对免疫系统的直接影响。我们研究了IFN-α对PBMC在树突状细胞（DC）分化方面的作用，因为PBMC在感染和癌症治疗期间暴露于高IFN-α水平。我们发现，在体外IFN-α的曝光诱导快速和强烈的DC成熟标志物CD 80，CD 86和CD 83在散装PBMC的上调。因此，IFN-α在24 h内诱导纯化的单核细胞上这些分子的上调。CD 80和CD 83表达的上调是IFN-α浓度依赖性的。与GM-CSF + IL-4产生的DC相反，大多数IFN-α激发的CD 83（+）细胞共表达单核细胞标记物CD 14。尽管具有典型的成熟DC免疫表型，但IFN-α处理的单核细胞保持吞噬活性，从未获得树突状形态。在混合淋巴细胞反应中，IFN-α处理的单核细胞比GM-CSF + IL-4诱导的DC更弱，但比未处理的单核细胞显著更强地诱导大量PBMC中的T细胞增殖。然而，只有GM-CSF + IL-4产生的DC能够诱导幼稚CD 4（+）T细胞的显著增殖。值得注意的是，当暴露于破伤风类毒素脉冲IFN-α处理的单核细胞时，自体记忆CD 4（+）T细胞增殖。与未处理或GM-CSF + IL-4暴露的单核细胞不同，IFN-α激发的单核细胞显示出持久的STAT-1磷酸化。值得注意的是，CD 83（+）CD 14（+）细胞存在于水痘皮损中，与IFN-α产生细胞密切接触。目前的研究结果表明，IFN-α单独迅速产生能够刺激记忆免疫应答的非树突状APC。这可能代表了IFN-α在体内的另一种作用模式。
IFN-alpha is a well-known agent for treatment of viral and malignant diseases. It has several modes of actions, including direct influence on the immune system. We investigated IFN-alpha effects on PBMC in terms of dendritic cell (DC) differentiation, as PBMC are exposed to high IFN-alpha levels during treatment of infections and cancers. We show that in vitro IFN-alpha exposure induced rapid and strong up-regulation of the DC-maturation markers CD80, CD86, and CD83 in bulk PBMC. Consistently, IFN-alpha induced up-regulation of these molecules on purified monocytes within 24 h. Up-regulation of CD80 and CD83 expression was IFN-alpha concentration-dependent. In contrast to GM-CSF + IL-4-generated DCs, most of the IFN-alpha-challenged CD83(+) cells coexpressed the monocyte marker CD14. Despite a typical mature DC immunophenotype, IFN-alpha-treated monocytes conserved phagocytic activity and never acquired a dendritic morphology. In mixed lymphocyte reactions IFN-alpha-treated monocytes were less potent than GM-CSF + IL-4-gencrated DCs but significantly more potent than untreated monocytes to induce T cell proliferation in bulk PBMC. However, only GM-CSF + IL-4-generated DCs were able to induce a significant proliferation of naive CD4(+) T cells. Notably, autologous memory CD4(+) T cells proliferated when exposed to tetanus toxoid-pulsed IFN-alpha-treated monocytes. At variance with untreated or GM-CSF + IL-4-exposed monocytes, those challenged with IFN-alpha showed long-lasting STAT-1 phosphorylation. Remarkably, CD83(+)CD14(+) cells were present in varicella skin lesions in close contact with IFN-alpha-producing cells. The present findings suggest that IFN-alpha alone promptly generates nondendritic APCs able to stimulate memory immune responses. This may represent an additional mode of action of IFN-alpha in vivo.