ENCEPHALITOZOAN CUNICULI--HOST IMMUNITY AND PATHOGENESIS

微孢子虫是一种专性的胞内原生动物寄生虫，可引起 艾滋病患者的机会性感染种类繁多。最多的 与艾滋病有关的常见微孢子虫、贝氏肠胞体虫、 会导致HIV感染者的慢性腹泻。然而，一个 目前还没有用于研究艾美耳球虫的动物模型。大多数 对微孢子虫进行了实验研究。 楔形脑炎吸虫。这种微孢子虫，通常感染 啮齿动物，在人类中也有报道。几份关于 HIV感染者中播散性楔形艾美耳球虫感染 最近才出现的。楔形棘球藻与其他 脑孢子虫和脑孢子虫等微孢子虫 肠道细菌，也是已知的引起艾滋病并发症的细菌 个人。对免疫机制知之甚少。 正常宿主的微孢子虫感染。细胞免疫 这似乎对保护小鼠免受E.cunceri挑战很重要。 初步研究表明CD8+T细胞是必不可少的组成部分 对免疫反应的影响。因此，CD8+T细胞的详细分析 免疫对于理解免疫保护机制是必不可少的。 抗楔形埃希氏菌感染。这个项目的第一个具体目标是 将评估CD8+T细胞反应的动力学 楔形艾美耳球虫感染病程。这一反应的区别在于 将确定耐药和敏感的小鼠物种之间的差异 比较；CD8+T细胞的细胞毒活性 将对受感染的正常动物和免疫受损动物进行检测。这个 第二个具体目标是确定领养人的效力 将免疫CD8+T细胞转移到受感染的免疫妥协宿主。 接下来，免疫CD8+T细胞可以保留的时间长度 它们在幼稚免疫受损宿主中的激活/记忆状态将 要下定决心。在第三个特定目标中，伽马/增量T的作用 细胞和CD4+T细胞在CD8+T细胞的诱导和维持中的作用 将对细胞免疫进行评估。这些研究将使 对其他微孢子虫免疫机制的外推，如 这是艾滋病患者更常遇到的一种疾病。

Microsporidia are obligate intracellular protozoan parasites which cause wide variety of opportunistic infections in AIDS patients. The most common microsporidium associated with AIDS, Enterocytozoon beneusi, causes chronic diarrhea in the HIV-infected individuals. However, an animal model for E. beneusi is not available at present. Most of the experimental studies on microsporidia have been carried out on with Encephalitozoon cuniculi. This microsporidium, which commonly infects rodents, has been reported in humans as well. Several reports of disseminated E. cuniculi infection in HIV-infected patients have appeared recently. E. cuniculi is also very closely related to other microsporidia like Encephalitozoon hellum and Encephalitozoon intestinalis, which are also known to cause complications in AIDS individuals. Very little is known about the immune mechanisms against microsporidial infection in the normal host. The cellular immunity appears to be important for protection against an E. cuniculi challenge. Preliminary studies suggest that CD8+ T cells are an essential component of the immune response. Therefore, the detailed analysis of CD8+ T cell immunity is essential for understanding the immunoprotective mechanism against E. cuniculi infection. The first specific aim in this project will be to evaluate the kinetics of CD8+ T cell response during the course of E. cuniculi infection. The difference in this response between the resistant and susceptible species of mice will be determined and compared; the cytotoxic activity of the CD8+ T cells from the infected normal and immunocompromised animals will be assayed. The second specific aim is to determine the efficacy of the adoptive transfer of immune CD8+ T cells into infected immunocompromise host. Next, the length of time for which the immune CD8+ T cells can retain their activated/memory state in the naive immunocompromised host will be determined. In the third specific aim the role of gamma/delta T cells and the CD4+ T cells in the induction and maintenance of CD8+ T cell immunity will be evaluated. These studies will enable extrapolation to the immune mechanisms against other microsporidia, like E. beneusi, which is more frequently encountered by AIDS patients.