| Project/Area Number |
09044265
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIMOTO Takayuki The University of Tokyo, Institute of Medical Sciencee, Assistant Professor, 医科学研究所, 助手 (80202406)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJI Moriya New York University School of Medicine, Associate Professor, 医学部, 助教授
NARIUCHI Hideo The University of Tokyo, Institute of Medical Sciencee, Professor, 医科学研究所, 教授 (10012741)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Malaria Infection / Host Resistance / Vaccine / IFN-gamma. / IL-12 / NO / Pathogenesis / Recombinant Virus / 組み替えウイルス / NK細胞 / マラリア / 感染防御 |
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| Research Abstract |
We have investigated the role of IL-12 in the development of host resistance to the bloodstage malaria infection and also in the pathogenesis using a lethal strain P.berghei NK65 and its irradiation-induced self-limiting strainP.berghei XAT.The P.berghei XAT infection induced IL-12 expression and resultant IFN-gamma production in spleen, which are important for the host resistance. On the other hand, the P.berghei NK65 infection also induced IL-12 expression and resultant IFN-gamma production in spleen and liver, which are rather important for the pathogenesis. Furthermore, the involvement of NK cells and NO, which are located downstream IL-12 and IFN-gamma, in the host resistance to P.berghei XAT infection has been shown not to be important although the infection with the self-limiting strain induced higher NK cell lytic activity and production of NO than that with the lethal strain. Other mechanism(s) involving IFN-gamma mainly produced by CD4^# T cells has been revealed to be important for the host resistance and remains to be elucidated. There seem to be two mechanisms which involves IFN-gamma and are functioning in early and late phases of the infection. One should be non-specific protection and another should be Ab-dependent Fc receptor-mediated phagocytosis or ADCC.These potential mechanisms are currently under investigation. We also have been trying to create an efficient way to induce the protective immunity to the liver-stage malaria infection, generated various recombinant viruses expressing CS proteins of P.yoelii or P.falciparum and compared their efficacy to produce anti-CS protein specific CD8^+ T cells. Single immunization of the recombinant adenovirus and priming with the recombinant influenza virus followed by a booster with the recombinant vaccinia virus have been shown to efficiently induce CD8^+ T cellmediated protective immunity against malaria, suggesting that these are very efficient way of vaccination against malaria infection.
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