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Identification of a novel protectiveantigen of Mycobacterium bovis and its application to the host defense

牛分枝杆菌新型保护性抗原的鉴定及其在宿主防御中的应用

基本信息

批准号：
06670285
负责人：
KAWAMURA Ikuo
金额：
$ 1.15万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670285/
关键词：
Mycobacterium Host defense Protective antigen Protective immunity Vaccine ワクチン Mycobacterium bovis BCG 感染抵抗性T細胞 BCG菌体抗原 IFNγ

项目摘要

The purpose of this study was to identify the protective antigen of Mycobacterium bovis BCG,which is critically important for the induction of IFN-gamma-producing protective CD4^+ T cells, and to determine the importance of this protective antigen in the expression of anti-tuberculosis immunity. The following results were obtained.1) In mice immunized with viable BVG,IFN-gamma-producing T cells were induced along with the protective immunity. In contrast, neither such T cells nor protective immunity could not be induced when immunization was done by killed BCG,though DTH reaction was generated. Among several fractions prepared from BCG cells, a 18 kDa antigen exhibited a marked ability to stimulate IFN-gamma production of BCG-immune spleen cells. This particular antigen was shown to be present not only in viable BCG or PPD but also in killed cells of BCG,suggesting that some factor other than antigen is involved in the induction of protective immunity of the host.2) T cell proliferatio … More n and IL-2 production were observed in BCG immune cells against a wide range of antigens with varying molecular weights, suggesting the insignificance of these paramenters as the establishment of protective immunity.3) We have determined the cytokine response of normal spleen cells after stimulation with viable or killed BCG.TNF-alpha expression was induced equally by both viable and killed BCG,while NO production was induced only by viable BCG.Viable cells of BCG was capable of inducing IFN-gamma in NK cells but killed BCG was not. NK cell-derived IFN-gamma appeared to be indispensable for iNOS expression. The difference of NO-inducing ability between viable and killed BCG seemed to be depending on the ability to induce IFN-gamma from NK cells. Considering the importance of IFN-gamma in the functional differentiation of Th1 type cells, it was suggested that the inability of killed BCG vaccine in the induction of protective immunity was attributable to the lack of IFN-gamma induction at the early stage of immunization. Less

本研究的目的是鉴定对诱导产生IFN-γ的保护性CD 4 ^+ T细胞至关重要的牛分枝杆菌BCG的保护性抗原，并确定这种保护性抗原在抗结核免疫表达中的重要性。1）在用活的BVG免疫的小鼠中，产生IFN-γ的T细胞被诱导沿着保护性免疫。而灭活BCG免疫则不能诱导这种T细胞，也不能诱导保护性免疫，但能产生DTH反应。在从BCG细胞制备的几种组分中，18 kDa抗原表现出显著的刺激BCG免疫脾细胞产生IFN-γ的能力。这种特殊的抗原不仅存在于活的BCG或PPD中，而且也存在于BCG的死细胞中，这表明除抗原外，还有其他因素参与诱导宿主的保护性免疫。 ...更多信息在BCG免疫细胞中观察到针对具有不同分子量的广泛抗原的TNF-α和IL-2的产生，表明这些参数对于建立保护性免疫无意义。3）我们已经确定了正常脾细胞在用活的或死的BCG刺激后的细胞因子应答。BCG活细胞能诱导NK细胞产生IFN-γ，而灭活BCG不能。NK细胞衍生的IFN-γ似乎是iNOS表达所必需的。活卡介苗和灭活卡介苗诱导NO能力的差异似乎取决于诱导NK细胞产生IFN-γ的能力。考虑到IFN-γ在Th 1型细胞功能分化中的重要性，有人认为灭活卡介苗不能诱导保护性免疫是由于在免疫早期缺乏IFN-γ诱导。少