IMMUNOLOGIC STUDIES ON SCHISTOSOMIASIS

该项目的目的是研究免疫机制， 血吸虫病免疫调节、免疫逃避和免疫病理学 最终目标是开发一种实验性疫苗， 人体试验和了解疾病的发病机制。 在今年完成的工作中，IL-10抑制 巨噬细胞介导的童虫杀伤被定义并显示为 这是由于抑制了TNF-α的合成。 此外，IL-10显示 与TGF-β和IL-4协同抑制两种幼虫 杀死和巨噬细胞产生氮氧化物代谢物。 小鼠肺组织细胞因子基因表达的PCR分析 在进行卵裂体虫卵肉芽肿形成时， IL-4、IL-2和IFN-γ在这个过程中。 在相关研究中， 发现Fcepsilon阳性的非B、非T细胞是主要的 感染者脾脏中抗原刺激的IL-4合成的来源 小鼠 最后，研究表明，受染色体感染的小鼠在免疫功能上有缺陷。 用重组牛痘构建体清除感染的能力 表达HIV-1的GP-160包膜蛋白。 这种病毒感染的减少 耐药性与Th 1细胞因子和CTL应答缺陷相关， 病毒

The aim of this project is to study mechanisms of immunity, immunoregulation, immune evasion, and immunopathology in schistosomiasis with the ultimate goals of developing an experimental vaccine suitable for human trials and understanding the pathogenesis of disease. In work completed this year, the mechanism by which IL-10 inhibits macrophage-mediated killing of schistosomula was defined and shown to be due to suppression of TNF-alpha synthesis. In addition, IL-10 was shown to synergize with TGF-beta and IL-4 in the inhibition of both larval killing and macrophage production of nitrogen oxide metabolites. An analysis by PCR of cytokine genes expressed in the lungs of mice undergoing schistosome egg granuloma formation revealed a central role for IL-4, IL-2, and IFN-gamma in this process. In related studies, it was discovered that Fcepsilon-positive non-B, non-T cells were the major source of antigen-stimulated IL-4 synthesis in the spleens of infected mice. Finally, schistosome-infected mice were shown to be defective in their ability to clear infections with a recombinant vaccinia construct expressing the GP-160 envelope protein of HIV-1. This decrease in viral resistance correlated with defects in the Th1 cytokine and CTL response to the virus.