Liposomal delivery of antigen to human dendritic cells

Liposomal delivery of antigen to human dendritic cells
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DOI:
10.1016/s0264-410x(02)00536-4
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发表时间:
2003-02-14
期刊:
影响因子:
5.5
通讯作者:
Davies, NM
Davies, NM
中科院分区:
医学3区
文献类型:
--
作者:
Copland, MJ;Baird, MA;Davies, NM

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本研究调查了与未修饰脂质体或溶液中的抗原制剂相比,甘露糖基化脂质体中的抗原制剂是否增强了树突状细胞(DC)的摄取和激活,并增加了DC诱导启动T细胞增殖的能力。用GM-CSF和IL-4培养外周血单核细胞生成未成熟人DC。用脂粒或含fitc偶联抗原的溶液孵育后,流式细胞术检测DC对抗原的摄取以及细胞表面标志物MHCⅱ类、CD80、CD86和DC成熟标志物CD83的表达程度。与暴露于溶液中的抗原相比,暴露于含有fitc卵清蛋白的脂质体导致细胞表面标记物的表达增强。暴露于甘露糖基化脂质体后表达最高。含有破伤风类毒素(TT)的甘露糖基化脂质体比TT中性脂质体或TT溶液更有效地刺激了启动T细胞的增殖。这项工作表明,甘露糖基化脂质体提供了一种多功能的递送载体,用于启动对包封肽或蛋白质疫苗的增强免疫反应。(C) 2002 Elsevier Science Ltd.版权所有。
This study investigated whether formulation of antigen in mannosylated liposomes enhanced uptake and activation of dendritic cells (DC) and increased the ability of DC to induce primed T cell proliferation compared to formulation of antigen in unmodified liposomes or in solution. Immature human DC were generated from peripheral blood monocytes cultured with GM-CSF and IL-4. Uptake of antigen by DC and the degree of expression of the cell surface markers MHC class II, CD80, CD86 and the DC maturation marker CD83, was investigated by flow cytometry following incubation with liposomes or solution containing FITC-conjugated antigen. Exposure to liposomes containing FITC-ovalbumin resulted in enhanced expression of cell surface markers when compared to exposure to antigen in solution. Expression was highest following exposure to mannosylated liposomes. Mannosylated liposomes containing tetanus toxoid (TT) stimulated primed T cell proliferation more effectively than TT-neutral liposomes or TT-solution. This work suggests that mannosylated liposomes provide a versatile delivery vehicle for initiating enhanced immune responses to encapsulated peptide or protein vaccines. (C) 2002 Elsevier Science Ltd. All rights reserved.