ANTIGEN-INDUCED APOPTOSIS (PROPRIOCIDAL REGULATION) OF MATURE T LYMPHOCYTES

我们发现，对成熟T细胞抗原受体的刺激 在细胞暴露于IL-2等促有丝分裂因子后 导致细胞程序性死亡或凋亡(本体型杀伤性 条例)。此过程可能会导致删除特定的 抗原反应性T细胞，不影响旁观者细胞。我们是 对这种效应的两个方面感兴趣：1)分子事件 发生，以及2)使用该机制的可能性 药物诱导消除与疾病有关的T细胞 流程。我们的结果表明，抗原诱导的细胞凋亡只能 发生在细胞周期的特定阶段。此外，我们还可以证明 适当的免疫将导致免疫抑制 反应性，很可能是因为特定的反应性T细胞 已经被淘汰了。 由过度刺激引起的几种疾病 免疫系统包括：过敏症、自身免疫性疾病等 硬化症和类风湿性关节炎，以及组织移植的排斥反应。 激活的T细胞是破坏性免疫背后的驱动力 对这些疾病的反应。目前的治疗方法包括药物，如 类固醇和环孢素A一般会损害T淋巴细胞 功能。因此，这些疗法的一个严重副作用是 增加感染的易感性。我们发现， 细胞因子IL-2能够导致特异性T细胞的死亡 通过它们的抗原受体刺激。这是以前未知的 IL-2的性质应该允许特定的消除某些 受体携带的T细胞可能成为新临床的基础 白介素2的应用。可以想象，导致疾病的T细胞 淋巴细胞可以被消除，而保留有帮助的T淋巴细胞。 因此，严重的免疫抑制是目前的副作用 治疗是可以避免的。谈话中，因为最近有证据表明 我们的体外实验表明，细胞凋亡可能是艾滋病患者CD4+T细胞丧失的原因 T细胞凋亡模型可能被证明是一个需要测试的重要系统 阻止细胞凋亡的药物。

We have found that stimulation of the antigen receptor of mature T cells following exposure of the cells to mitogenic lymphokines such as IL-2 leads to the induction of programmed cell death or apoptosis (propriocidal regulation). This process can lead to the deletion of specific antigen-reactive T cells without affecting bystander cells. We are interested in two aspects of this effect: 1) the molecular events that take place, and 2) the possibility of using this mechanism to pharmacologically induce the elimination of T cells involved in disease processes. Our results indicate that antigen-induced apoptosis can only occur at specific stages of the cell cycle. Moreover, we can demonstrate that appropriate immunization will lead to the suppression of immune responsiveness, most likely because the specifically reactive T cells have been eliminated. Several types of diseases that arise from the over-stimulation of the immune system including: allergies, autoimmune disorders such as multiple sclerosis and rheumatoid arthritis, and the rejection of tissue grafts. Activated T cells are the driving force behind the destructive immune response in these diseases. Current therapies involve drugs such as steroids and cyclosporin A that impair, in a general way, T lymphocyte function. Therefore, one serious side effect of these therapies is to increase susceptibility to infections. We have discovered that the cytokine IL-2 is able to cause the death of T cells that are specifically stimulated through their antigen receptor. This previously unknown property of IL-2 should allow the specific elimination of certain receptor-bearing T cells which could form the basis for new clinical applications of IL-2. It is conceivable that disease-causing T lymphocytes could be eliminated while sparing helpful T lymphocytes. Thus, the severe immunosuppression which is a side-effect of current therapies could be avoided. Conversly, because of the recent evidence that apoptosis may underly the loss of CD4+ T cells in AIDS, our in vitro model of T cell apoptosis may prove to be an important system to test for drugs that block apoptosis.