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Type-1 polarized dendritic cell vaccine for tuberculosis

1 型极化树突状细胞结核疫苗

基本信息

批准号：
21590986
负责人：
NAKAMURA Yutaro
金额：
$ 2.83万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590986/
关键词：
免疫学感染症細胞ワクチン免疫細胞・組織細胞,組織

项目摘要

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. Recently, we found that more preferable DCs were generated by the presence of IL-4 and IFN-γduring 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 ; DC1), and with LPS alone(non-polarized DCs ; DC). DCs were loaded with listeriolysin O(LLO) 91-99, H2-K^d-restricted epitope of L. monocytogenes, and were injected into naive BALB/c mice intravenously. Type-1 polarized DCs vaccine strongly enhanced LLO 91-99-specific CD8^+T cells exhibiting epitope-specific cytotoxic activity and IFN-γproduction, 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.

开发有效的细胞内细菌（包括结核病）疫苗策略是医学研究的主要前沿之一。我们之前的研究表明，树突状细胞（DC）疫苗是一种很有前途的方法，可以激发对细胞内细菌的保护性免疫。最近，我们发现在小鼠dc（1型极化）成熟过程中，IL-4和IFN-γ的存在产生了更理想的dc，从而提高了肿瘤抗肿瘤免疫的诱导。本研究表明，这种1型极化dc可显著增强对细胞内单核增生李斯特菌的保护性免疫。用LPS、IL-4和IFN-γ（1型极化DC； DC1）和单独LPS（非极化DC； DC）培养小鼠骨髓源性DC并使其成熟。将dc负载李斯特菌溶素O(LLO) 91-99和单增李斯特菌H2-K^d限制性表位，并静脉注射到BALB/c小鼠体内。1型极化dc疫苗强烈增强llo91 -99特异性CD8^+T细胞，表现出表位特异性细胞毒活性和IFN-γ的产生，从而显著诱导对单核增生乳杆菌的保护性免疫。1型极化dc是增强保护性免疫的潜在候选者，可用于设计针对细胞内细菌的有效疫苗接种策略。