CELLULAR BIOLOGY AND IMMUNOLOGY OF LEISHMANIASIS

我们的长期目标是分析一个 新近发现的T细胞介导的新机制 巨噬细胞抗利什曼效应在宿主防御中的激活 在活体内。这种激活机制涉及抗原特异性。 效应T细胞与感染的巨噬细胞之间的相互作用 既不是由淋巴因子介导的，也不是 对宿主细胞的细胞毒性。不同研究充分的小鼠模型 将对利什曼病进行调查，以努力确定 人血清白蛋白的体外表达是否存在相关性 淋巴因子非依赖性激活机制(称为 “接触媒介”)和小鼠感染的解决。作为一名 推论，抑制细胞(或其可溶细胞) 产品)来自BALB/c小鼠的播散性主要乳杆菌 感染可下调小鼠体内效应T细胞的表达 我们将探索体外实验。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激活机制 将他们对氧化爆发的依赖程度与 体外产生抗利什曼效应及其影响 对吞噬菌体pH的影响。最后，小鼠巨噬细胞的激活 化验将适用于人类细胞培养，以允许后续 临床研究。一种新型T细胞介导型细胞的研究 巨噬细胞抗菌防御的激活机制 预计与利什曼病有直接关系，以及 对理解宿主有潜在的重要影响 对某些细胞内病原体的防御。因为这部小说 防御机制涉及小鼠淋巴细胞的一个亚类 类似于人类感染艾滋病毒的人，这条线的结果 可能与患者的感染并发症有关的调查 得了艾滋病。

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.