Analysis of induction and activation mechanism of protective CD8 T cells against pulmonary tuberculosis and application for the development of anti-tuberculosis vaccine

肺结核保护性CD8 T细胞诱导激活机制分析及其在抗结核疫苗研制中的应用

• 批准号: 18590431
• 负责人: MATSUZAKI Goro
• 金额: $ 2.65万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590431/
• 关键词: Mycobacterium; immunity; CD8+T cell; antigenic peptide; host defence to bacteria; CD8T細胞

Although importance of CD8+T cells in protection against pulmonary tuberculosis has been reported using CD8-depleted or CD8+T cell-deficient mice, it is not clear how migration and activation of the mycobacterial Ag-specific T cells are regulated in the Mycobacterium tuberculosis (Mtb)-infected lung. To address the issue, we generated pentamer of MHC H-2D^b and mycobacterial Ag Mtb32a epitope complex (D^<b->Mtb32a 5mer). Using the reagent we identified mycobacterial Mtb32a-specific CD8+T cells from day 21 in the lung and from day 28 in the mediastinal lymph node after Mtb lung infection. In contrast, Mycpbacterium bovis BCG, a vaccine strain, also express Mtb32a epitope identical to that of Mtb, and BCG subcutaneous infection induced D^b-Mtb32a 5mer-stained CD8+T cells from day 7 which is earlier than that observer after Mtb lung infection. When BCG vaccinated mice were infected with Mtb in the lung 30 days after the vaccination, induction of Mtb32a-specific CD8+T cells in the lung accelerated and clearly detected from day 7 after the infection. Furthermore, the increase of the Mtb32a-specificT cells parallel to increase of interferon-gamma production in the lung in response to Mtb32a peptide. The results suggest that induction of Mtb-specific CD8+T cells delays in the lung of Mtb-infected lung, and BCG vaccination accelerate the induction with interferon-gamma production.

尽管已经使用CD 8-耗尽或CD 8 +T细胞缺陷小鼠报道了CD 8 +T细胞在预防肺结核中的重要性，但尚不清楚结核分枝杆菌（Mtb）感染的肺中如何调节分枝杆菌Ag特异性T细胞的迁移和活化。为了解决这个问题，我们产生了MHC H-2D_b和分枝杆菌Ag Mtb 32a表位复合物的五聚体（<b->D_Mtb32a 5 mer）。使用该试剂，我们从Mtb肺部感染后第21天起在肺中以及从第28天起在纵隔淋巴结中鉴定了分枝杆菌Mtb 32a特异性CD 8 +T细胞。相比之下，疫苗株牛Mycpbacterium bovis BCG也表达与Mtb相同的Mtb 32a表位，并且BCG皮下感染从第7天开始诱导D^b-Mtb 32a 5 mer染色的CD 8 +T细胞，这比Mtb肺部感染后的观察者早。当接种BCG疫苗的小鼠在接种后30天在肺中感染Mtb时，肺中Mtb 32a特异性CD 8 +T细胞的诱导加速，并且从感染后第7天起清楚地检测到。此外，Mtb 32a特异性T细胞的增加与肺中响应于Mtb 32a肽的干扰素-γ产生的增加平行。结果表明，诱导结核分枝杆菌特异性CD 8 +T细胞在结核分枝杆菌感染的肺延迟，和卡介苗接种加速诱导与干扰素-γ的生产。

项目成果

Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice.

• DOI: 10.1016/j.vaccine.2007.12.005
• 发表时间: 2008-02
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: H. Kohama;M. Umemura;Y. Okamoto;A. Yahagi;H. Goga;T. Harakuni;G. Matsuzaki;T. Arakawa

IL-17-mediated regulation of innate and acquired immune response against pulmonary mycobacterial infection

IL-17介导的针对肺部分枝杆菌感染的先天和获得性免疫反应的调节

• 发表时间: 2007
• 作者: Begum;M.D.;Umemura.M.;Kon;S.;Yahagi;A.;Hamada;S.;Oshiro;K.;Gotoh;K.;Nishizono;A.;Uede;T.;Matsuzaki;G.;梅村 正幸;梅村 正幸;梅村 正幸
• 通讯作者: 梅村 正幸

Importance of murine Vδ1+ γδ T cells expressing interferon-γ and interleukin-17A in innate protection against Listeria monocytogenes infection

• DOI: 10.1111/j.1365-2567.2008.02841.x
• 发表时间: 2008-10-01
• 期刊: IMMUNOLOGY
• 影响因子: 6.4
• 作者: Hamada, Satoru;Umemura, Masayuki;Matsuzaki, Goro
• 通讯作者: Matsuzaki, Goro

IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacilli Calmette-Guerin

IL-17介导的针对肺分枝杆菌卡介苗的先天性和获得性免疫反应的调节

• 发表时间: 2007
• 期刊: Journal of Immunology 178・6
• 作者: Umemura;M.;Yahagi;A.;Hamada;S.;Begum;M. D.;Watanabe;H.;Kawakami;K.;Suda;T. Sudo;K.;Nakae;S.;Iwakura;Y.;Matsuzaki;G.;Masayuki Umemura
• 通讯作者: Masayuki Umemura

Suppression of the bacterial antigen-specific T cell response and the dendritic cell migration to the lymph nodes by osteopontin

• DOI: 10.1111/j.1348-0421.2007.tb03884.x
• 发表时间: 2007-01-01
• 期刊: MICROBIOLOGY AND IMMUNOLOGY
• 影响因子: 2.6
• 作者: Begum, Mst. Dilara;Umemura, Masayuki;Matsuzaki, Goro
• 通讯作者: Matsuzaki, Goro