Parlato S, Santini S M, Lapenta C, Di Pucchio T, Logozzi M, Spada M, Giammarioli A M, Malorni W, Fais S, Belardelli F
Laboratory of Virology, Laboratory of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Blood. 2001 Nov 15;98(10):3022-9. doi: 10.1182/blood.v98.10.3022.
The migration capability of dendritic cells (DCs) is regulated by their response to factors, namely chemokines, that characterize maturation stage and shape their functional activities. This study examines the morphology, expression of chemokines/chemokine receptors, and migration properties of DCs generated after treatment of monocytes with type I interferon (IFN) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (IFN-DCs). IFN-DCs showed phenotypical and morphologic features undetectable in DCs generated in the presence of interleukin 4 (IL-4) and GM-CSF, such as expression of CD83 and CD25 and the presence of CD44+, highly polarized, thin, and long dendrites. IFN-DCs markedly migrated in response to beta-chemokines (especially MIP-1beta) and expressed the Th-1 chemokine IP-10. Notably, IFN-DCs showed an up-regulation of CCR7 as well as of its natural ligand MIP-3beta, characteristics typical of mature DCs. Of interest, IFN-DCs exhibited a marked chemotactic response to MIP-3beta in vitro and strong migratory behavior in severe combined immunodeficient (SCID) mice. In SCID mice reconstituted with human peripheral blood leukocytes, IFN-DCs induced a potent primary human antibody response and IFN-gamma production, indicative of a Th-1 immune response. These results define the highly specialized maturation state of IFN-DCs and point out the existence of a "natural alliance" between type I IFN and monocyte/DC development, instrumental for ensuring an efficient connection between innate and adaptive immunity.
树突状细胞（DC）的迁移能力受其对某些因子（即趋化因子）的反应调节，这些趋化因子表征成熟阶段并塑造其功能活性。本研究检测了用I型干扰素（IFN）和粒细胞巨噬细胞集落刺激因子（GM-CSF）处理单核细胞后产生的DC的形态、趋化因子/趋化因子受体表达及迁移特性（IFN-DC）。IFN-DC表现出在白细胞介素4（IL-4）和GM-CSF存在下产生的DC中未检测到的表型和形态学特征，如CD83和CD25的表达以及CD44+、高度极化、细长的树突的存在。IFN-DC对β趋化因子（尤其是MIP-1β）有明显迁移反应，并表达Th-1趋化因子IP-10。值得注意的是，IFN-DC显示CCR7及其天然配体MIP-3β上调，这是成熟DC的典型特征。有趣的是，IFN-DC在体外对MIP-3β表现出明显的趋化反应，在严重联合免疫缺陷（SCID）小鼠中表现出强烈的迁移行为。在用人类外周血白细胞重建的SCID小鼠中，IFN-DC诱导了强烈的原发性人类抗体反应和IFN-γ产生，表明存在Th-1免疫反应。这些结果定义了IFN-DC高度特化的成熟状态，并指出I型IFN与单核细胞/DC发育之间存在“天然联盟”，有助于确保先天免疫和适应性免疫之间的有效联系。
