CELLULAR BIOLOGY AND IMMUNOLOGY OF LEISHMANIASIS

长期目标是分析 最近发现的T细胞介导的 宿主防御中巨噬细胞抗利什曼效应的激活 in vivo. 这种激活机制涉及抗原特异性 效应T细胞和感染的巨噬细胞之间的相互作用， 既不是淋巴因子介导的，也不涉及 对宿主细胞的细胞毒性。 不同的经过充分研究的小鼠模型 将对利什曼病进行调查， 体外表达与细胞凋亡之间是否存在关联 非淋巴因子依赖性激活机制（称为 “接触介导的”）和小鼠感染的消退。 作为 推论，抑制细胞（或其可溶性 产品）的BALB/c小鼠与播散性L.主要 感染可以下调效应T细胞的表达， 将进行体外研究。 在相关研究中，淋巴因子介导的 和细胞接触介导的巨噬细胞活化机制 将比较它们对氧化爆发的依赖性， 在体外赋予抗利什曼原虫作用，以及它们的影响 最后，小鼠巨噬细胞活化 试验将适用于人细胞培养物， 临床研究。 这些关于一种新的T细胞介导的 巨噬细胞抗菌防御机制激活可以 预期与利什曼病有直接关系， 对理解宿主具有潜在的重要意义 防御某些其他细胞内病原体。 自从这本小说 防御机制涉及小鼠淋巴细胞的一个亚类 与人类感染HIV的病毒类似， 调查可能与患者的感染并发症有关 艾滋病

The long-term objective is to analyze the potential role of a recently-identified novel mechanism of T cell-mediated activation of macrophage antileishmanial effects in host defense in vivo. This mechanism of activation involves antigen-specific interactions between effector T cells and infected macrophages, interactions that are neither lymphokine-mediated nor involve cytotoxicity to host cells. Different well-studied murine models of leishmaniasis will be investigated in an effort to establish whether a correlation exists between the in vitro expression of the lymphokine-independent activation mechanism (referred to as "contact-mediated") and resolution of infection in mice. As a corollary, the possibility that suppressor cells (or their soluble products) from BALB/c mice with disseminated L. major infections can down-regulate expression of the effector T cells in vitro will be explored. In related studies, lymphokine-mediated and cell contact-mediated mechanisms of macrophage activation will be compared for their dependence on an oxidative burst to impart an antileishmanial effect in vitro, and for their influence on phagolysosomal pH. Finally, the murine macrophage activation assay will be adapted to human cell cultures to permit subsequent clinical studies. These studies of a novel T cell-mediated mechanism activation of macrophage antimicrobial defense can be expected to have direct relevance to leishmaniasis as well as have potentially important implications for understanding host defense to certain other intracellular pathogens. Since this novel defenes mechanism involves a subclass of murine lymphocytes analogous to those infected by HIV in humans, results of this line of investigation could bear on infectious complications in patients with AIDS.