Intratracheal injection of dendritic cells loaded with cytotoxic T cell epitope of intracellular pathogen efficiently induces epitope-specific T cells and confers protective immunity

本研究旨在研制一种有效的黏膜细胞疫苗，以对抗细胞内病原体的感染。用单核细胞增生性李斯特菌溶血素O的优势细胞毒性T细胞(CTL)表位LLO91-99冲击小鼠骨髓来源的树突状细胞16h。然后，向气管内注入负载LLO的树突状细胞。气管内注射负载LLO的树突状细胞诱导四聚体确定的LLO特异性CTL，以及区域淋巴结产生LLO特异性干扰素-γ。在肺部LM感染的小鼠模型中，接种疫苗的小鼠与未接种的小鼠相比，细菌剂量显著减少。此外，这种树突状细胞疫苗保护他们免受致命的LM感染。综上所述，这些结果表明，气管内接种携带针对细胞内病原体的优势CTL表位的树突状细胞是一种有效的粘膜疫苗，它既能诱导黏膜部位的保护性免疫，又能诱导全身免疫。

The present study was conducted to develop an effective mucosal cell-vaccine against infection of intracellular pathogen. Bone-marrow derived mouse dendritic cells were treated with LPS for 16 hrs, and pulsed with dominant cytotoxic T cell (CTL) epitope, LLO91-99, derived from lysteriolysin O of Listeria monocytogenesis (LM). Then, LLO-loaded dendritic cells were intratracheally instilled. Tracheal injection of LLO-loaded dendritic cells induced LLO-specific CTL determined by tetramers, and LLO-specific IFN-gamma production from regional lymph nodes. In a mouse model of pulmonary LM infection, vaccinated mouse showed a significant decrease in bacterial doses compared with naive mouse. Moreover, this dendritic cell-vaccine protected them from lethal LM infection. Taken together, these results suggest that intratracheal administration of dendritic cells loaded with a dominant CTL epitope against intracellular pathogen is an effective mucosal vaccine, which induces protective immunity the mucosal sites as well as systemic immunity.