Project/Area Number |
01570210
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
寄生虫学(含医用動物学)
|
Research Institution | Gunma University |
Principal Investigator |
WAKI Seiji Gunma University School of Medicine Department of Parasitology Associate Professor, 医学部, 助教授 (10056286)
|
Co-Investigator(Kenkyū-buntansha) |
小野 久米夫 群馬大学, 医学部, 助手 (00211144)
田辺 和裄 大阪工業大学, 一般教育科, 助教授 (40047410)
|
Project Period (FY) |
1989 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
|
Keywords | Malaria / Plasmodium berghei / Immunity / Pathogenesis / INF-gamma / TNF-alpha / IgG isotype / 抗体 / 好中球 / 顆粒球コロニ-刺激因子(GーCSF) / インタ-フェロンガンマ-(IFNーγ) / 腫瘍壊死因子(TNFーα) / Tリンパ球 / インタ-フェロン / 腫瘍壊死因子(TNF) / ガンマ-インタ-フェロン / TNF / lgG2aアイソタイプ |
Research Abstract |
Immunity to malaria was investigated in mice using two strains of rodent plasmodia, one was virulent Plasmodium berghei and another one was an attenuated mutant strain. The infection of mice with virulent P. berghei was always lethal. The treatment with anti-CD8^+ or anti-IFN-gamma delayed the mortality of the infected mice, although it did not affect the parasite growth. In the late stage of the infection, T cells, especially CD8^+ T cells, were increased in number in the liver at the expense of splenic CD8^+ T cells. The mononuclear cells including CD8^+ T cells isolated from the liver released IFN-gamma and TNF-alpha in culture. These results suggest that these cytokines produced by the immune response may be responsible for pathogenesis of malaria. An attenuated mutant of P. berghei caused a resolving infection in mice. In mice infected with the parasites, CD4^+ T cells had a crucial role in protective immunity. INF-gamma produced from CD4^+ T cells was the key molecule in protective
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immunity. Mice injected with human recombinant G-CSF showed increased neutrophil count in the blood. Effect of the treatment with G-CSF on the attenuated P. berghei infection was suppressive, but anti-INF-gamma interfered with the effect. The results suggest neutrophils may be one of effector cells and INF-gamma may be involved in protection. Development of anti-plasmodial IgG2a in infected mice was suppressed by the treatment with anti-INF-gamma. Passive transfer of an IgG2a fraction from immune serum was capable of transferring protection. The results indicate that production of protective IgG2a antibodies may be dependent on INF-gamma. In conclusion, T cells stimulated with malaria antigen play important roles In conclusion, T cells stimulated with malaria antigen play important roles both in protection and pathogenesis depending upon their subsets; CD8^+ T cells in pathogenesis and CD4^+ T cells in protective immunity. These apparently contradictory responses may be mediated by the same cytokine, INF-gamma. Less
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