IMMUNE REGULATION IN TOXOPLASMOSIS AND OTHER OPPORTUNISTIC INFECTIONS

点击翻译按钮获取中文摘要

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.