IMMUNE REGULATION IN TOXOPLASMOSIS AND OTHER OPPORTUNISTIC INFECTIONS

该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，以确定 哪些细胞免疫成分和寄生虫靶抗原 参与控制感染及其分解， 免疫受损的宿主 今年在以下领域取得了进展： 1. 超抗原反应性T细胞在小鼠免疫反应中的无能诱导 感染 先前表征的V β 5 + T细胞群体 扩展为T。弓形虫超抗原活性被证明是 特别是在从急性到慢性的过渡期间， 感染 2. T.弓形虫 单核因子诱导活性。 霸王弓形虫分子负责 IL-12、IL-10、IL-13和TNF-γ诱导显示为热稳定的 蛋白酶敏感性和依赖性不同的糖缀合物 宿主蛋白激酶C 3. IFN-γ和IL-10基因敲除小鼠对T. 弓形虫感染 IFN-γ合成缺陷的小鼠显示， 由于未能控制寄生虫而迅速死于感染 生长，而IL-10敲除小鼠也迅速死亡， 促炎细胞因子的过度产生，而不是增加 寄生虫水平。 4. HIV+ T细胞中寄生虫诱导的IFN-γ和IL-12合成缺陷 感染刚地虫的病人 当用速殖子提取物刺激时，PBMC 来自T.弓形虫感染率 缺乏IFN-γ和IL-12应答，同时产生正常水平的 其他寄生虫诱导的单核因子。

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.