1999 Fiscal Year Final Research Report Summary
Studies on development of schistosomiasis vaccine by using gene-manipulated mice
| Project/Area Number |
10470066
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
寄生虫学(含医用動物学)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KOJIMA Somei Inst. Med. Sci., Dept. Parasitol., The University of Tokyo, Professor, 医科学研究所, 教授 (00009622)
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| Co-Investigator(Kenkyū-buntansha) |
HAYANO Masashi Inst. Med. Sci., Dept. Parasitol., The University of Tokyo, Res. Associate, 医科学研究所, 助手 (10272329)
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| Project Period (FY) |
1998 – 1999
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| Keywords | schistosomiasis / protective immunity / gene-manipulated mice / vaccine / cytokine |
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| Research Abstract |
Effector mechanisms involved in protective immunity to schistosome infections were studied by using various inbred and gene-manipulated mice. A significant reduction in worm recovery was observed in DBA/2 vaccinated with γ-irradiated cercariae, whereas C57BL/6 and BALB/c showed no, detectable level of protection against challenge infection with S.japonicum. Spleen cells of vaccinated C57BL/6 mice produced lower levels of Th1 cytokines compared to the cells of BALB/c and DBA/2, while production of Th2 cytokines was higher in BALB/c than in the other two strains. Macrophages that had been stimulated with splenocyte culture supernatants derived from vaccinated DBA/2 damaged schistosomula more effectively than the cells stimulated with supernatants from the other strains. These results suggest that different levels of protection observed among mouse strains depend on the balance of Th1/Th2 cytokine responses which consequently activate or suppress macrophage-mediated damage to schistosomul
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a. Furthermore, IRF-1 seemed to be essential to induce protective immunity, since significant reduction of worm recovery was observed in vaccinated wild type (WT) but nth in IRF-1ィイD1+ィエD1 (KO) mice. Both vaccinated WT and KO mouse splenocytes produced comparable levels of Th2 cytokines upon stimulation with worm antigens. On the contrary, IFN-γ production of KO mice was extremely lower than that of WT mice. In addition, mouse eosinophils from IL-5 transgenic mice showed lower killing activity against schistosomula if compared to rat eosinophils. A large number of rat eosinophils adhered to schistosomula during culture, whereas a few mouse cells did. Determination of EPO and superoxide showed positive correlation between schistosomulicidal activity and the production as well as the secretion of these substances. These results suggest that the low schistosomulicidal activity of mouse eosinophils is not only due to the lower ability of the cells to larvae, but also due to the low content of toxic substances produced by the cells. Less
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