Antigen Delivery to Plasmacytoid Dendritic Cells via BST2 Induces Protective T Cell-Mediated Immunity
Antigen Delivery to Plasmacytoid Dendritic Cells via BST2 Induces Protective T Cell-Mediated Immunity
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DOI：
10.4049/jimmunol.1004029
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发表时间：
2011-06-15
影响因子：
4.4
通讯作者：
Krug, Anne B.
中科院分区：
文献类型：
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作者：
Loschko, Jakob;Schlitzer, Andreas;Krug, Anne B.
浆细胞样树突状细胞 (PDC) 能够以耐受性或免疫原性方式将 Ag 呈递给 T 细胞，具体取决于 Ag 的配方和刺激模式。尚未研究体内针对 PDC 的 Ab 介导的 Ag 是否可以诱导可用于疫苗接种的有效适应性免疫反应。在这项研究中，我们发现，通过骨髓基质细胞Ag 2 (BST2)/CD317与作为佐剂的TLR激动剂组合，将Ag递送至小鼠PDC，由PDC在体内特异性呈递，并引发强烈的细胞和体液免疫反应。其中包括 CD4(+) T 细胞产生的 IFN-γ 以及具有多种 IgG 同种型的高抗体滴度。此外，在聚肌苷-聚胞苷酸作为佐剂存在的情况下，BST2介导的Ag递送可诱导在体内发挥功能的细胞毒性T淋巴细胞。使用Ag融合抗BST2抗体与作为佐剂的聚肌苷-聚胞苷酸进行单次免疫足以触发针对随后的病毒感染和肿瘤生长的保护性免疫。我们的结论是，尽管 PDC 具有潜在的耐受性，但靶向 PDC 的 Ag 与作为佐剂的 TLR 激动剂相结合是一种有效的疫苗接种策略。免疫学杂志，2011，186：6718-6725。
Plasmacytoid dendritic cells (PDCs) are capable of presenting Ags to T cells in a tolerogenic or immunogenic manner depending on the formulation of the Ag and the mode of stimulation. It has not been investigated whether effective adaptive immune responses useful for vaccination can be induced by Ab-mediated Ag targeting to PDCs in vivo. In this study, we show that Ag delivered to murine PDCs via bone marrow stromal cell Ag 2 (BST2)/CD317 in combination with TLR agonists as adjuvants is specifically presented by PDCs in vivo and elicits strong cellular and humoral immune responses. These include IFN-gamma production by CD4(+) T cells and high Ab titers with a broad range of IgG isotypes. In addition, BST2-mediated Ag delivery in the presence of polyinosinic-polycytidylic acid as adjuvant induces cytotoxic T lymphocytes that are functional in vivo. A single immunization with Ag-fused anti-BST2 Ab together with polyinosinic-polycytidylic acid as adjuvant is sufficient to trigger protective immunity against subsequent viral infection and tumor growth. We conclude that despite the potential tolerogenic properties of PDCs, Ag targeting to PDCs in combination with TLR agonists as adjuvants is an effective vaccination strategy. The Journal of Immunology, 2011, 186: 6718-6725.