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

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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