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， 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： A. 弓形虫超抗原活性的证明。 速殖子被证明具有分子， 增殖和IFN-γ的合成 未感染的动物 这项活动，它满足了所有的主要 超抗原的标准，可能有助于解释早期诱导 T.弓形虫和遗传学 对疾病的易感性。 B。 IL-12在先天性抵抗中的作用。 IL-12的诱导是 显示出对于早期IFN-γ依赖性抗性至关重要， 小鼠急性感染，但不太重要或非必要的 预防疾病复发。 C. T.刚地。 的 T.显示弓形虫 不依赖于巨噬细胞脂蛋白受体，但涉及类似的 信号转导途径 T.弓形虫被证明能够 在病毒感染的人单核细胞中刺激HIV复制，或 来自含有整合的前病毒的转基因小鼠的巨噬细胞。

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: A. Demonstration of a superantigen activity in Toxoplasma gondii. Tachyzoites were shown to possess molecule(s) which stimulate proliferation of and IFN-gamma synthesis by splenocytes from uninfected animals. This activity, which fulfills all of the major criteria of a superantigen, may help explain both the early induction of cell-mediated immunity by T. gondii and the genetics of susceptibility to disease. B. Role of IL-12 in innate resistance. The induction of IL-12 was shown to be critical for the early IFN-gamma-dependent resistance of mice to acute infection but less important or non-essential for the prevention of disease reactivation. C. Studies on mechanisms of monokine induction by T. gondii. The triggering of the monokines TNF-alpha and IL-12 by T. gondii was shown to be independent of macrophage Lps receptors but to involve a similar signal transduction pathway. T. gondii was shown to be capable of stimulating HIV replication in virally infected human monocytes or macrophages from transgenic mice containing integrated provirus.