THE IMMUNOBIOLOGY OF HIV INDUCED T-CELL AND MONOCYTE DYSFUNCTION

为了了解是什么导致与艾滋病相关的免疫崩溃，我们正在 HIV及其包膜对T细胞和巨噬细胞影响的研究 在体外发挥作用。我们观察到艾滋病毒既有抑制性，也有 对T细胞和巨噬细胞功能的刺激作用 与触发这些细胞的试剂同时进行。单元格 激活标记CD26已被证明在 单核细胞嗜单核细胞病毒进入并似乎导致细胞功能障碍 以及为细胞凋亡做好准备。我们检查了艾滋病毒感染的影响 对巨噬细胞分泌细胞因子(IL-10、IL-12和TNF)的影响。病毒 感染本身并不能诱导细胞因子的分泌，而是间接的 根据细胞的启动状态调节因子的产生。 我们的研究结果支持免疫功能紊乱的发病机制模型 是由病毒的直接作用和间接作用引起的 细胞因子。在这些研究过程中，我们报告了这种分泌物 细胞因子IL-12参与p40和p40的协同表达 IL-12的P35链。人类免疫缺陷病毒及细胞因子对血管紧张素系统影响的研究 免疫细胞功能对了解慢性支气管炎的免疫发病机制具有重要意义 艾滋病毒和评估艾滋病和疫苗的生物效应 治疗。 海斯，M.P.，王，J.和诺克罗斯，M.A.白介素12的调节 人单核细胞的表达：干扰素-γ选择性启动 脂多糖诱导的p35和p40基因。《血色1995》；86：646-650。

To understand what causes immune collapse associated with AIDS, we are studying the effects of HIV and its envelope on T-cell and macrophage function in vitro. We have observed that HIV has both inhibitory and stimulatory activities on T-cell and macrophage function when presented simultaneously with reagents which trigger these cells. The cell activation marker CD26 has been shown to play an important role in monocytotropic virus entry and appears to contribute to cell dysfunction and cell priming for apoptosis. We examined the effects of HIV infection on cytokine secretion (IL-10, IL-12, and TNF) in macrophages. Virus infection alone does not induce cytokine secretion but indirectly modulates factor production depending on the primed status of the cell. Our results support a model of pathogenesis in which immune dysfunction is caused by both direct viral effects and indirect effects mediated by cytokines. In the course of these studies, we reported that secretion of the cytokine IL-12 involves coordinated expression of both the p40 and p35 chains of IL-12. Studies on the effects of HIV and cytokines on immune cell function is important to understanding immunopathogenesis of HIV and to evaluating the biological effects of AIDS and vaccine therapies. Hayes, M.P., Wang, J., and Norcross, M.A. Regulation of Interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes. Blood 1995; 86: 646-650.