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Study on the role of IL-12 in protective immunity against infection

IL-12在感染保护性免疫中的作用研究

基本信息

批准号：
09044265
负责人：
YOSHIMOTO Takayuki
金额：
$ 2.5万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

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.

我们研究了IL-12在宿主对血期疟疾感染的抵抗力形成中的作用，以及在致死株伯氏疟原虫NK65及其辐射诱导的自限菌株P.berghei Xat的致病机制中的作用。伯氏疟原虫Xat感染诱导了IL-12的表达，并在脾中产生了干扰素-γ，这对宿主抵抗是重要的。另一方面，伯氏假单胞菌NK65感染也可诱导脾、肝IL-12的表达和干扰素-γ的产生，这在发病机制中起着重要作用。此外，位于IL-12和干扰素-γ下游的NK细胞和NO参与宿主对伯氏疟原虫XAT感染的抵抗力并不重要，尽管自限株感染比致死株诱导更高的NK细胞裂解活性和NO产生。另一种机制(S)涉及主要由CD4T细胞产生的干扰素-γ，已被发现在宿主抵抗中起重要作用，但仍有待阐明。似乎有两种机制涉及干扰素-γ，并在感染的早期和晚期发挥作用。一种应该是非特异性保护，另一种应该是抗体依赖的Fc受体介导的吞噬作用或ADCC。这些潜在的机制目前正在研究中。我们还试图创造一种有效的方法来诱导对肝期疟疾感染的保护性免疫，制备了表达约氏疟原虫和恶性疟原虫CS蛋白的各种重组病毒，并比较了它们产生抗CS蛋白特异性CD8^+T细胞的效果。重组腺病毒单独免疫和重组流感病毒免疫后再用重组痘苗病毒加强免疫均能有效诱导CD8~+T细胞介导的抗疟疾保护性免疫，是一种非常有效的抗疟疾免疫方法。