II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany.
J Immunol. 2011 Jun 15;186(12):6718-25. doi: 10.4049/jimmunol.1004029. Epub 2011 May 9.
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-γ 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.
浆细胞样树突状细胞 (PDCs) 能够以耐受原或免疫原性方式将抗原呈递给 T 细胞，具体取决于抗原的配方和刺激方式。目前还没有研究过通过抗体介导的抗原靶向 PDC 能否在体内诱导有效的适应性免疫反应，从而用于疫苗接种。在本研究中，我们表明，通过骨髓基质细胞抗原 2 (BST2)/CD317 与 TLR 激动剂联合作为佐剂将抗原递送至小鼠 PDC 中，可在体内由 PDC 特异性呈递，并引发强烈的细胞和体液免疫反应。这些反应包括 CD4(+) T 细胞产生 IFN-γ 和具有广泛 IgG 同种型的高抗体滴度。此外，在多聚肌苷酸-多聚胞苷酸作为佐剂存在的情况下，BST2 介导的抗原递呈可诱导体内功能的细胞毒性 T 淋巴细胞。单次免疫接种融合了抗 BST2 Ab 的抗原，再加上多聚肌苷酸-多聚胞苷酸作为佐剂，足以引发针对随后的病毒感染和肿瘤生长的保护性免疫。我们得出结论，尽管 PDC 具有潜在的耐受原性，但将抗原靶向 PDC 与 TLR 激动剂联合作为佐剂是一种有效的疫苗接种策略。
