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牛分枝杆菌 BCG 的保护性抗原，该抗原对于诱导产生 IFN-γ 的保护性 CD4^+ T 细胞至关重要，并确定该保护性抗原在抗 BCG 表达中的重要性。 -结核病免疫。1)在用活的BVG免疫的小鼠中，产生IFN-γ的T细胞与保护性免疫一起被诱导，相反，当用活的BVG免疫时，既不能诱导这样的T细胞，也不能诱导保护性免疫。通过灭活的 BCG 进行免疫，但在由 BCG 细胞制备的几种级分中，18 kDa 的抗原显示出具有刺激 BCG 免疫脾细胞产生 IFN-γ 的显着能力。不仅存在于活的 BCG 或 PPD 中，而且存在于被杀死的 BCG 细胞中，这表明除抗原之外的某些因素也参与了宿主保护性免疫的诱导。2) T 细胞增殖 … 更多 n 和在 BCG 免疫细胞中观察到针对不同分子量的多种抗原的 IL-2 产生，表明这些参数作为保护性免疫的建立并不重要。 3) 我们已经确定了正常脾细胞在用活细胞刺激后的细胞因子反应。活体和灭活的 BCG 均诱导 TNF-α 表达，而仅活体 BCG 诱导 NO 产生。BCG 的活体细胞能够在 NK 细胞中诱导 IFN-γ，但灭活的 BCG 则不能NK 细胞来源的 IFN-γ 似乎对于 iNOS 表达是不可或缺的。考虑到 IFN 的重要性，活的和灭活的 BCG 之间的 NO 诱导能力似乎取决于从 NK 细胞诱导 IFN-γ 的能力。 γ-γ在Th1型细胞功能分化中的作用，提示灭活卡介苗不能诱导保护性免疫，可能是由于免疫早期缺乏IFN-γ诱导所致。较少的