Enhanced antigen presentation and CTL activity by transduction of mature rather than immature dendritic cells with octaarginine-modified liposomes
Enhanced antigen presentation and CTL activity by transduction of mature rather than immature dendritic cells with octaarginine-modified liposomes
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DOI：
10.1016/j.jconrel.2009.01.004
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发表时间：
2009-05-21
影响因子：
10.8
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
--
作者：
Homhuan, Atthachai;Kogure, Kentaro;Harashima, Hideyoshi
为了提高树突状细胞（DCs）对外源性抗原（Ag）的摄取和交叉提呈，采用辛托宁修饰的脂质体（R8-Lip）作为蛋白-Ag转导的新策略。未成熟DC有效地内吞大分子。虽然成熟的DC失去了它们捕获Ag的能力，但具有增加的T细胞活化能力。因此，Ag转导主要在未成熟DC中进行。在本研究中，R8-Lip被未成熟和成熟DC有效摄取。成熟后转导的DC在交叉呈递Ag方面是高效的，并且诱导比成熟前转导的DC更高的细胞毒性T淋巴细胞（CTL）活性。Ag的呈递机制涉及R8-Lip从内体逃逸到胞质溶胶，这需要酸性环境。然后通过蛋白酶体依赖性途径处理释放的Ag。这种新的转导方法是临床上适用的，易于执行，并具有比目前的蛋白质转导方法更实际的优势。(C)2009 Elsevier B. V.保留所有权利。
To improve uptake and cross-presentation of exogenous antigens (Ag) by dendritic cells (DCs), octaarginine-modified liposomes (R8-Lip) were used as a novel strategy for protein-Ag transduction. Immature DCs endocytose macromolecules efficiently. While mature DCs lose their ability to capture Ag, but have an increased capacity for T-cell activation. Thus Ag-transduction has been performed mostly in immature DCs. In the present study, R8-Lip were efficiently taken up by both immature and mature DCs. DCs transduced after maturation were highly efficient at cross-presentation of Ag and induced higher cytotoxic T-lymphocytes (CTL) activity than were DCs transduced before maturation. The mechanism of Ag presentation involved the escape of R8-Lip from endosomes to cytosol, which require the acidic environment. The Ag released was then processed by a proteasome-dependent pathway. This novel transduction approach is clinically applicable, easy to perform, and has more practical advantages than current protein transduction methods. (C) 2009 Elsevier B.V. All rights reserved.