著者

牧野 正彦

出版者

日本ハンセン病学会

雑誌

日本ハンセン病学会雑誌 (ISSN:13423681)

巻号頁・発行日

vol.82, no.3, pp.107-110, 2013 (Released:2016-06-30)

参考文献数

10

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A novel recombinant BCG (BCG-DHTM), that was deficient in urease, expressed with gene encoding the fusion of BCG-derived HSP70 and M. tuberculosis-derived major membrane protein (MMP)-Ⅱ, was constructed for use as a vaccine against tuberculosis. BCG-DHTM efficiently activated dendritic cells (DC) to induce cytokine production, including IL-12, TNFα and IL-1β and phenotypic changes. The DC infected BCG-DHTM was more potent in activation of naïve T cells of CD4 and CD8 subsets than those infected vector control BCG. The activation of naïve T cells by BCG-DHTM was closely associated with phagomal maturation, and that of naïve CD8+ T cells by BCG-DHTM was induced by the activation of cytosolic cross-presentation pathway. Further, BCG-DHTM seemed to activate naïve CD4+ T cells and naïve CD8+ T cells by antigen-specific fashion. The primary infection of BCG-DHTM in C57BL/6 mice for 12 weeks efficiently produced T cells responsive to in vitro secondary stimulation with MMP-Ⅱ HSP70 and H37Rv-derived cytosolic protein and inhibited with multiplication of subsequently challenged M. tuberculosis in lungs at least partially.   The effect of BCG-DHTM as a vaccine for tuberculosis is not fully convincing and need the improvement, however, our strategy in the development of new recombinant BCG for tuberculosis seems to provide useful tool.