| Project/Area Number |
11670307
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | KINKI UNIVERSITY |
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Principal Investigator |
MIYAZAWA Masaaki KINKI UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (60167757)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Hiroyuki KINKI UNIVERSITY, SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (80309335)
TABATA Nobutada KINKI UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (40298948)
MATSUMURA Haruo KINKI UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (10229536)
UDAKA Keiko KYOTO UNIVERSITY, GRADUATE SCHOOL OF SCIENCE, ASSOCIATE PROFESSOR, 大学院・理学研究科, 助教授 (40263066)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | RETROVIRUS / VACCINE / TLYMPHOCYTE / EPITOPE / LEUKEMIA / CYTOTOXICITY / NATURAL KILLER CELL / IMMUNE PROTECTION / ペプチド / エピトープ / CD4陽性Tリンパ球 / CD8陽性Tリンパ球 / 細胞傷害性Tリンパ球 / 抗体 |
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| Research Abstract |
We have previously shown that immunization with a synthetic peptide that contains a single CD4^+ T-cell epitope protects highly susceptible mice against immunosuppressive Friend retrovirus infection. Cells producing infectious Friend virus were rapidly eliminated from the spleen of mice that had been immunized with the single- epitope peptide. However, actual effector mechanisms induced through T-helper cell responses after Friend virus inoculation were unknown. When cytotoxic effector cells detected in the early phase of Friend retrovirus infection were separated based on their expression of cell surface markers, those lacking CD4 and CD8 but expressing natural killer cell markers were found to constitute the majority of effector cells that lysed Friend virus-induced leukemia cells. Depletion of natural killer cells by injecting anti-asialo GM_1 antibody did not affect the number of CD4^+ or CD8^+ T cells in the spleen, virus antigen-specific proliferative responses of CD4^+ T cells,
… More
or cytotoxic activity against Friend virus-induced leukemia cells exerted by CD8^+ effector cells, but completely abolished the effect of peptide immunization. Although the above enhancement of natural killer cell activity in the early stage of Friend virus infection was also observed in mice given no peptide, these results have demonstrated the importance and requirement of natural killer cells in the vaccine-induced resistance against the retroviral infection.
Other sets of cell-depletion and transfer experiments also showed that CD4^+ and CD8^+ T cells were required for the vaccine-induced protection against Friend retrovirus infection, and the presence of CD4^+ T cells was absolutely required for the production, but not just class switching, of virus-neutralizing antibodies. Thus, these results clearly show that a single-epitope CD4^+ T cell vaccine induces immune resistance against Friend retrovirus infection by rapidly activating multiple effector mechanism soon after the virus infection including CD4^+ and CD8^+ cytotoxic effector cells, virus-neutralizing antibodies, and NK cells. Less
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