Malaghan Institute of Medical Research, Wellington, New Zealand.
PLoS One. 2011 Mar 31;6(3):e17657. doi: 10.1371/journal.pone.0017657.
Transfer of antigen between antigen-presenting cells (APCs) is potentially a physiologically relevant mechanism to spread antigen to cells with specialized stimulatory functions. Here we show that specific CD8+ T cell responses induced in response to intravenous administration of antigen-loaded bone marrow-derived dendritic cells (BM-DCs), were ablated in mice selectively depleted of endogenous lymphoid-resident langerin+ CD8α+ dendritic cells (DCs), suggesting that the antigen is transferred from the injected cells to resident APCs. In contrast, antigen-specific CD4+ T cells were primed predominantly by the injected BM-DCs, with only very weak contribution of resident APCs. Crucially, resident langerin+ CD8α+ DCs only contributed to the priming of CD8+ T cells in the presence of maturation stimuli such as intravenous injection of TLR ligands, or by loading the BM-DCs with the glycolipid α-galactosylceramide (α-GalCer) to recruit the adjuvant activity of activated invariant natural killer-like T (iNKT) cells. In fact, injection of α-GalCer-loaded CD1d-/- BM-DCs resulted in potent iNKT cell activation, suggesting that this glycolipid antigen can also be transferred to resident CD1d+ APCs. While iNKT cell activation per se was independent of langerin+ CD8α+ DCs, some iNKT cell-mediated activities were reduced, notably release of IL-12p70 and transactivation of NK cells. We conclude that both protein and glycolipid antigens can be exchanged between distinct DC species. These data suggest that the efficacy of DC-based vaccination strategies may be improved by the incorporation of a systemic maturation signal aimed to engage resident APCs in CD8+ T cell priming, and α-GalCer may be particularly well suited to this purpose.
抗原呈递细胞（APCs）之间的抗原转移是一种潜在的生理相关机制，可以将抗原传播到具有特殊刺激功能的细胞中。在这里，我们表明，通过静脉内给予负载抗原的骨髓衍生树突状细胞（BM-DC），在选择性耗尽内源性淋巴组织驻留 langerin+CD8α+树突状细胞（DC）的小鼠中，诱导的特定 CD8+T 细胞反应被消除，这表明抗原从注射细胞转移到驻留 APC。相比之下，抗原特异性 CD4+T 细胞主要由注射的 BM-DC 诱导，驻留 APC 的贡献非常微弱。至关重要的是，驻留的 langerin+CD8α+DC 仅在成熟刺激物（如静脉内注射 TLR 配体）存在下或通过加载 BM-DC 以招募激活的不变自然杀伤样 T（iNKT）细胞的佐剂活性的情况下，才有助于 CD8+T 细胞的初始。事实上，注射α-半乳糖基神经酰胺（α-GalCer）负载的 CD1d-/-BM-DC 导致强烈的 iNKT 细胞活化，表明这种糖脂抗原也可以转移到驻留的 CD1d+APC。虽然 iNKT 细胞的活化本身独立于 langerin+CD8α+DC，但一些 iNKT 细胞介导的活性降低，特别是 IL-12p70 的释放和 NK 细胞的转活化。我们得出结论，蛋白质和糖脂抗原可以在不同的 DC 之间交换。这些数据表明，通过纳入旨在使驻留 APC 参与 CD8+T 细胞初始的全身性成熟信号，基于 DC 的疫苗接种策略的疗效可能得到改善，并且α-GalCer 可能特别适合于此目的。
