MOLECULAR PATHWAYS INVOLVED IN THE PROGRAMMED DEATH OF LYMPHOCYTES

很明显，一个内部死亡计划 控制体内免疫细胞的数量和类型。 疾病可由低效的淋巴细胞死亡或由 不适当的或过度的死亡，如由人类引起的 艾滋病期间感染免疫缺陷病毒(HIV)。在这个项目中，我们是 从多方面研究分子机制 在淋巴细胞中的这种死亡程序。我们的攻击是基于 一种名为CD95/Fas/APO-1的细胞表面受体模型 在刺激免疫细胞死亡方面起着重要作用。我们 正试图了解这种受体是如何刺激 导致细胞死亡的细胞内机制。尤其是我们 专注于一种名为Flice/Mach1的蛋白酶的激活 (Caspase 8)，可以直接执行死亡程序。这些 研究将帮助我们确定细胞如何启动它们自己的 死亡，它的调节可能在各种疾病中发挥作用 从自身免疫性疾病到艾滋病等传染病。 感染艾滋病毒后，艾滋病发病的关键影响因素 据信是由病毒引起的T淋巴细胞死亡。我们 想要确定为什么病毒会触发T细胞的死亡。

It has become clear that an internal death program controls the number and types of immune cells in the body. Diseases can result from inefficient lymphocyte death or from inappropriate or excessive death such as is caused by the human immunodeficiency virus (HIV) during AIDS. In this project we are taking a multifaceted approach to studying molecular mechanisms of this death program in lymphocytes. Our attack is based on the model of a cell surface receptor called CD95/Fas/APO-1 that can play an important role in stimulating the death of immune cells. We are trying to understand how this receptor stimulates the intracellular machinery that causes cellular demise. In particular we have focused on the activation of a protease termed Flice/Mach1 (caspase 8) which can directly carry out the death program. These studies will help us to determine how cells can initiate their own death whose regulation may play a role in various diseases ranging from autoimmune conditions to infectious diseases such as AIDS. Following infection with HIV, a critical effect in the onset of AIDS is believed to be death of T lymphocytes caused by the virus. We would like to determine why the virus triggers the death of T cells.