IMMUNE REGULATION IN TOXOPLASMOSIS AND OTHER OPPORTUNISTIC INFECTIONS

这个项目的总体目标是分析免疫反应 弓形虫和其他机会性感染，以便确定 哪些细胞免疫成分和寄生虫靶抗原是 参与控制感染及其在年的细分 免疫功能受损的宿主。 今年在以下方面取得了进展： 1.小鼠超抗原反应性T细胞无能的诱导 感染。先前描述的Vbeta5+T细胞群 经弓形虫超抗原扩增后的活性显示 特别是在从急性到慢性的转变过程中 感染。 2.弓形虫的生化特性及其对PKC的依赖性 单核细胞因子诱导活性。弓形虫的分子负责 IL-12、IL-10、IL-13和肿瘤坏死因子-γ的诱导具有热稳定性 不同蛋白水解酶敏感度和依赖性的糖偶联物 关于宿主蛋白--蛋白激酶C。 3.干扰素-γ和IL-10基因敲除小鼠对T。 弓形虫感染。干扰素-γ合成有缺陷的小鼠被证明 由于未能控制寄生虫而迅速死于感染 在生长的同时，IL-10基因敲除的小鼠也迅速死亡，因为 促炎细胞因子的过度产生而不是增加 寄生虫水平。 4.缺陷寄生虫诱导HIV+T细胞合成干扰素-γ和IL-12。 感染了弓形虫的患者。当用速殖子提取物刺激时，PBMC 从HIV+弓形虫血清阳性者中发现 缺乏干扰素-γ和IL-12反应，同时产生正常水平的 其他寄生虫诱导的单核细胞。

The overall aim of this project is to analyze the immune response to Toxoplasma gondii and other opportunistic infections in order to define which cellular immune components and parasite target antigens are involved in the control of infection and its breakdown in immunocompromised hosts. Progress was made this year in the following areas: 1. Induction of anergy in superantigen reactive T cells during murine infection. A previously characterized population of Vbeta5+ T cells expanded by a T. gondii superantigen activity was shown to be specifically anergized during the transition from acute to chronic infection. 2. Biochemical characterization and PKC dependence of T. gondii monokine-inducing activities. The T. gondii molecules responsible for IL-12, IL-10, IL-13 and TNF-gamma induction were shown to be heat-stable glyconjugates which differ in their protease sensitivity and dependence on host protein-kinase C. 3. Increased susceptibility of IFN-gamma and IL-10 knockout mice to T. gondii infecitons. Mice defective in IFN-gamma synthesis were shown to rapidly succumb to infection because of a failure to control parasite growth while IL-10 knockout mice also rapidly died because of the overproduction of proinflammatory cytokines rather than increased parasite levels. 4. Defective parasite-induced IFN-gamma and IL-12 synthesis in HIV+ T. gondii-infected patients. When stimulated with tachyzoite extracts, PBMC from HIV+ individuals seropositive for T. gondii were shown to mount deficient IFN-gamma and IL-12 responses while producing normal levels of other parasite-induced monokines.