THE IMMUNOBIOLOGY OF HIV INDUCED T-CELL DYSFUNCTION

为了了解艾滋病中免疫系统崩溃的原因， 研究HIV和包膜对T细胞功能的影响 体外功能 我们发现，艾滋病毒除了抑制T- 细胞功能，在呈递时对T细胞具有强效刺激活性 与触发T细胞受体的试剂同时使用。 包络 蛋白质增强T细胞增殖和IL-2产生。 这 “共刺激”活性似乎在幼稚外周T细胞上最活跃， 这可能解释了在CD 4和CD 8中看到的免疫激活 HIV感染者的T细胞亚群。 我们目前要求 HIV介导的共刺激是否能诱导异常的细胞因子调节 导致免疫功能紊乱 结果表明 HIV感染过程中病毒介导的信号可能导致 病毒抑制和共刺激作用，它们一起破坏了 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的免疫发病机制很重要， 评估基于整个HIV的疫苗的生物效应， 重组包膜蛋白。

To understand what causes immune collapse seen in AIDS, we are investigating the functional effects of HIV and envelope on T-cell function in vitro. We have found that HIV, in addition to inhibiting T- cell function, has potent stimulatory activity on T-cells when presented simultaneously with regents which trigger the T-cell receptor. Envelope proteins potentiate both T-cell proliferation and IL-2 production. 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 which is responsible for immune dysfunction. The results indicate that virus mediated signals in the course of HIV infection may lead to both viral inhibitory and costimulatory effects which together disrupt 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 vaccines based on whole HIV and recombinant envelope proteins.