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Studies on malaria immunology

疟疾免疫学研究

基本信息

批准号：
01570210
负责人：
WAKI Seiji
金额：
$ 1.41万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

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 … More 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 rolesIn 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

用伯氏强毒疟原虫和减毒突变株两株鼠疟原虫对小鼠进行了疟疾免疫试验。抗CD8+或抗-干扰素-γ治疗虽然不影响寄生虫的生长，但可延缓感染小鼠的死亡率。在感染后期，肝内T细胞，尤其是CD8~+T细胞数量增加，而脾中CD8~+T细胞减少。从肝脏分离的单个核细胞，包括CD8~+T细胞，在培养过程中释放出干扰素-γ和肿瘤坏死因子-α。这些结果表明，免疫反应产生的这些细胞因子可能与疟疾的发病机制有关。伯氏疟原虫的减毒突变株在小鼠中引起了溶解感染。在感染寄生虫的小鼠中，CD4^+T细胞在保护性免疫中起着至关重要的作用。CD4^+T细胞产生的干扰素-γ是保护…的关键分子更多的豁免权。注射人重组G-CSF的小鼠血液中中性粒细胞数量增加。G-CSF对减毒伯氏杆菌感染有抑制作用，而抗-干扰素-γ则有干扰作用。结果提示，中性粒细胞可能是效应细胞之一，而干扰素-γ可能参与了保护作用。抗-干扰素-γ治疗可抑制感染小鼠体内抗疟原虫IgG2a的形成。被动转移免疫血清中的IgG2a组分可传递保护性免疫。结论疟疾抗原刺激的T细胞根据其亚群的不同在免疫保护和发病机制中发挥重要作用，CD8^+T细胞在发病机制中起重要作用，而CD4^+T细胞在保护性免疫中起重要作用。这些明显相互矛盾的反应可能是由相同的细胞因子--干扰素-γ介导的。较少