Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice.
Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice.
复制标题
I型干扰素是单核细胞衍生的树突状细胞发育和体外和HU-PBL-SCID小鼠活性的强大佐剂。
DOI：
10.1084/jem.191.10.1777
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发表时间：
2000-05-15
影响因子：
15.3
通讯作者：
Belardelli, F
中科院分区：
文献类型：
--
作者：
Santini, S M;Lapenta, C;Logozzi, M;Parlato, S;Spada, M;Di Pucchio, T;Belardelli, F
I型干扰素（IFN）是表现出抗病毒和抗肿瘤作用的细胞因子，包括对免疫细胞的多种活性。然而，这些细胞因子在导致免疫应答产生的早期事件中的重要性仍不清楚。在这里，我们研究了I型干扰素对新鲜分离的粒细胞/巨噬细胞集落刺激因子（GM-CSF）处理的人单核细胞在树突状细胞（DC）的分化和活性在体外和严重的联合免疫缺陷小鼠与人外周血白细胞（人PBL-SCID）小鼠重建的影响。I型IFN诱导单核细胞出人意料地快速成熟为短寿命的肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）表达DC，其被赋予有效的功能活性，相对于白细胞介素（IL）-4/GM-CSF处理而言上级，如通过FACS®分析、用同种异体PBL的混合白细胞反应测定和对HIV-1脉冲的自体DC的淋巴细胞增殖应答所示。I型IFN诱导IL-15产生并强烈促进T辅助细胞1型反应。值得注意的是，在用自体PBL重建的SCID小鼠中注射IFN处理的HIV-1脉冲的DC导致产生有效的初次免疫应答，如通过检测针对各种HIV-1抗原的人抗体所评估的。这些结果提供了使用I型IFN作为疫苗佐剂的基本原理，并支持这些细胞因子和单核细胞/DC之间的天然联盟代表了连接先天性免疫和适应性免疫的重要早期机制的概念。
Type I interferons (IFNs) are cytokines exhibiting antiviral and antitumor effects, including multiple activities on immune cells. However, the importance of these cytokines in the early events leading to the generation of an immune response is still unclear. Here, we have investigated the effects of type I IFNs on freshly isolated granulocyte/macrophage colony-stimulating factor (GM-CSF)–treated human monocytes in terms of dendritic cell (DC) differentiation and activity in vitro and in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) mice. Type I IFNs induced a surprisingly rapid maturation of monocytes into short-lived tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)–expressing DCs endowed with potent functional activities, superior with respect to the interleukin (IL)-4/GM-CSF treatment, as shown by FACS® analyses, mixed leukocyte reaction assays with allogeneic PBLs, and lymphocyte proliferation responses to HIV-1–pulsed autologous DCs. Type I IFN induced IL-15 production and strongly promoted a T helper cell type 1 response. Notably, injection of IFN-treated HIV-1–pulsed DCs in SCID mice reconstituted with autologous PBLs resulted in the generation of a potent primary immune response, as evaluated by the detection of human antibodies to various HIV-1 antigens. These results provide a rationale for using type I IFNs as vaccine adjuvants and support the concept that a natural alliance between these cytokines and monocytes/DCs represents an important early mechanism for connecting innate and adaptive immunity.