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

气管内注射负载细胞内病原体细胞毒性T细胞表位的树突状细胞，可有效诱导表位特异性T细胞并赋予保护性免疫

• 批准号: 17590784
• 负责人: SUDA Takafumi
• 金额: $ 2.24万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590784/
• 关键词: Dendritic cell; Mucosal vaccine; Listeria; リステリア; 結核; ワクチン

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.

本研究旨在研制一种有效的抗细胞内病原体感染的粘膜细胞疫苗。用LPS处理骨髓来源的小鼠树突细胞16小时，并用来源于单核细胞生成李斯特菌（LM）的溶血素O的显性细胞毒性T细胞（CTL）表位LLO 91 -99脉冲。然后，将负载LLO的树突状细胞进行气管内滴注。气管注射负载LLO的树突状细胞诱导由四聚体确定的LLO特异性CTL，以及局部淋巴结产生的LLO特异性IFN-γ。在肺部LM感染的小鼠模型中，与未接种小鼠相比，接种小鼠显示细菌剂量显著降低。此外，这种树突状细胞疫苗可以保护他们免受致命的LM感染。总之，这些结果表明，肠道内施用负载有针对细胞内病原体的优势CTL表位的树突状细胞是有效的粘膜疫苗，其诱导粘膜部位的保护性免疫以及全身免疫。

项目成果

Quantitative analysis of fibroblastic foci in usual interstitial pneumonia

• DOI: 10.1378/chest.130.1.22
• 发表时间: 2006-07-01
• 期刊: CHEST
• 影响因子: 9.6
• 作者: Enomoto, Noriyuki;Suda, Takafumi;Chida, Kingo
• 通讯作者: Chida, Kingo

Identification of HLAA*0201-Restricted T-Cell Epitope on MPT51 Protein, a Major Secreted Protein Derived from Mycobacterium tuberculosis using MPT5 1 Overlappin, Peptides Screening.

使用 MPT5 1 Overlappin、肽筛选鉴定 MPT51 蛋白（结核分枝杆菌衍生的主要分泌蛋白）上的 HLAA*0201 限制性 T 细胞表位。

• 发表时间: 2008
• 期刊: Infect Immun (in press)
• 作者: Aoshi T;Nagata T;Suzuki M;et. al.
• 通讯作者: et. al.

Correlation between peripheral blood T-cell profiles and airway inflammation in atopic asthma.

外周血 T 细胞谱与特应性哮喘气道炎症之间的相关性。

• 发表时间: 2006
• 期刊: J Allergy Clin Immunol 118
• 作者: Shirai T;Inui N;Suda T;et. al.
• 通讯作者: et. al.

alpha-Galactosylceramide, a ligand of natural killer T cells, inhibits allergic airway inflammation.

• 发表时间: 2005
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4
• 作者: H. Matsuda;T. Suda;J. Sato;T. Nagata;Y. Koide;K. Chida;Hirotoshi Nakamura

Lung dendritic cells have a potent capability to induce production 0f immunoglobulin A.

肺树突状细胞具有诱导产生 0f 免疫球蛋白 A 的强大能力。

• 发表时间: 2008
• 期刊: Am J Respir Cell Mol Biol 38
• 作者: Naito T;Suda T;Suzuki K;et. al.
• 通讯作者: et. al.