THE IMMUNOBIOLOGY OF HIV INDUCED T-CELL DYSFUNCTION

为了了解是什么导致了艾滋病的免疫崩溃，我们正在 人类免疫缺陷病毒及其包膜对T细胞和T细胞的影响 巨噬细胞的体外功能。我们观察到艾滋病毒既有 对T细胞功能的抑制和共刺激活性 与触发T细胞受体的试剂同时进行。这 “共刺激”活动似乎在幼稚的外围设备上最为活跃 T细胞，这可能解释了在CD_4和CD_4中所见的免疫激活 HIV感染者T细胞CD8亚群的研究我们目前正在 问HIV介导的共刺激是否能诱导异常细胞因子 调节和促进免疫功能障碍。在这种情况下，我们是 病毒感染对T细胞和巨噬细胞影响的研究 细胞因子的产生。结果表明，病毒具有多效性。 导致细胞因子产生减少或增加的信号 从而扰乱免疫系统的正常平衡功能 导致艾滋病。这些研究对于理解 HIV的免疫致病机制及其生物学效应的评价 以扭转免疫死亡为目标的艾滋病和疫苗疗法。

To understand what causes immune collapse seen in AIDS, we are investigating the effects of HIV and its envelope on T-cell and macrophage function in vitro. We have observed that HIV has both inhibitory and costimulatory activities on T-cell function when presented simultaneously with reagents which trigger the T-cell receptor. This "costimulatory" activity appears to be most active on naive peripheral T-cells and may explain the immune activation seen in both the CD4 and CD8 subsets of T-cells in HIV infected individuals. We are currently asking whether HIV mediated costimulation can induce abnormal cytokine regulation and contribute to immune dysfunction. In this context, we are studying the effects of virus infection on both T cell and macrophage cytokine production. The results indicate that virus mediates pleiotropic signals that result in either reduced or enhanced cytokine production thereby disrupting the normal balanced function of the immune system leading to AIDS. These studies are important to understanding the immunopathogenesis of HIV and to evaluating the biological effects of AIDS and vaccine therapies targeted at reversing immunological demise.