Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Vaccine. 2012 Mar 30;30(16):2633-9. doi: 10.1016/j.vaccine.2012.02.026. Epub 2012 Feb 22.
The development of effective vaccine strategies for intracellular bacteria, including tuberculosis, is one of the major frontiers of medical research. Our previous studies showed that dendritic cell (DC) vaccine is a promising approach for eliciting protective immunity against intracellular bacteria. However, it has been reported that standard fully mature DCs show reduced ability to produce IL-12p70 upon subsequent interaction with antigen (Ag)-specific T cells, limiting their in vivo performance for vaccines. Recently, we found that such "DC exhaustion" could be prevented by the presence of IL-4 and IFN-γ during the maturation of mouse DCs (type-1 polarization), resulting in improved induction of anti-tumor immunity in cancer. Here we show that such type-1 polarized DCs promote dramatic enhancement of protective immunity against an intracellular bacterium, Listeria monocytogenes. Murine bone marrow-derived DCs were cultured and matured with LPS, IL-4 and IFN-γ (type-1 polarized DCs), and with LPS alone (non-polarized DCs). DCs were loaded with listeriolysin O (LLO) 91-99, H2-K(d)-restricted epitope of L. monocytogenes, and were injected into naïve BALB/c mice intravenously. Type-1 polarized DCs produced significantly higher levels of IL-12p70 than non-polarized DCs in vitro, and this vaccine strongly enhanced LLO 91-99-specific CD8(+) T cells exhibiting epitope-specific cytotoxic activity and IFN-γ production, leading to significant induction of protective immunity against L. monocytogenes. Type-1 polarized DCs are potential candidates for enhancing protective immunity in the design of effective vaccination strategies against intracellular bacteria.
针对包括结核分枝杆菌在内的胞内细菌，开发有效的疫苗策略是医学研究的主要前沿领域之一。我们之前的研究表明，树突状细胞（DC）疫苗是诱导针对胞内细菌保护性免疫的一种很有前途的方法。然而，据报道，标准的完全成熟的 DC 在与抗原（Ag）特异性 T 细胞随后相互作用时，产生 IL-12p70 的能力降低，限制了它们在体内作为疫苗的性能。最近，我们发现，在小鼠 DC 成熟过程中（1 型极化）存在 IL-4 和 IFN-γ 可以防止这种“DC 衰竭”，从而改善对癌症的抗肿瘤免疫诱导。在这里，我们显示这种 1 型极化的 DC 可显著增强对胞内细菌李斯特菌的保护性免疫。用 LPS、IL-4 和 IFN-γ（1 型极化的 DC）和单独 LPS（非极化的 DC）培养和成熟鼠骨髓来源的 DC。用李斯特菌溶血素 O（LLO）91-99、H2-K（d）限制性李斯特菌表位负载 DC，并通过静脉内注射到 naive BALB/c 小鼠中。1 型极化的 DC 在体外产生的 IL-12p70 水平明显高于非极化的 DC，这种疫苗强烈增强了 LLO 91-99 特异性 CD8（+）T 细胞，表现出表位特异性细胞毒性活性和 IFN-γ 产生，导致对李斯特菌的保护性免疫的显著诱导。1 型极化的 DC 是增强针对胞内细菌的保护性免疫的潜在候选者，可用于设计有效的疫苗接种策略。
