INDUCTION OF SPECIFIC IMMUNE TOLERANCE

描述：(改编自调查者摘要)：免疫系统是 负责抗击疾病的主要生物防御系统。然而， 免疫反应也可能是有害的。在移植的情况下， 尽管免疫系统做出了适当的反应，但它还是会通过 破坏移植的器官。在自身免疫性疾病中，免疫系统 转而攻击自己并攻击其他正常组织。在这两种情况下，它 对于暂停免疫系统的破坏性功能是很重要的 维持正常的免疫反应。目前，在临床情况下， 诱导全身免疫抑制，患者对 感染性挑战受到损害。目前正在寻求的战略是 成功地诱导特定的无反应(耐受性)而不影响 免疫功能正常。 免疫系统的重要细胞是T细胞。它们控制着许多免疫系统 并作为效应器细胞。他们的镇压对 诱导耐受性。仅与给定器官反应的细胞，例如 移植或自身免疫性疾病的靶点应被移除。AS 不同类型的细胞表达组织特异性抗原，完全耐受 朝向给定组织的方向，最好是由该组织本身诱导。这应该是 对于移植排斥反应和自身免疫性疾病也是如此。一直以来都是 认为自身免疫性疾病背后的疾病机制与 可见于移植排斥反应。因此，应该有可能适应 诱导特异性移植耐受治疗的策略 自身免疫性疾病。 所谓的否决效应(常规否决权)已被证明是有效和 特别耐受T细胞。它通过共受体的表达发挥作用 刺激细胞表面CD8的表达。基于这一原始观察，该方法具有 已经扩展到混合抗体(Hab)的开发，它结合了一种 以CD4或CD9功能区为靶向抗体部分 辅助分子。包被这些赤潮毒素的细胞抑制了激活。 以一种高度特异的方式激活CD4+或CD8+。在当前 应用，建议检测CD8的功能和活性 器官移植动物模型中的靶向血凝素。

DESCRIPTION: (Adapted from the Investigator's abstract): The immune system is the major biological defense system responsible for fighting disease. However, immune responses can also be detrimental. In the case of transplantation, although the immune system reacts appropriately, it nevertheless causes harm by destroying the transplanted organs. In autoimmune diseases, the immune system turns against self and attacks otherwise normal tissue. In both situations, it is important to suspend the destructive function of the immune system while maintaining normal immune responses. Presently, in the clinical situation, a general immune suppression is induced, and the patients' defenses against infectious challenges are impaired. Strategies are now being sought that successfully induce specific non-responsiveness (tolerance) without affecting normal immune functions. Important cells of the immune system are T cells. They control many immune responses and also act as effector cells. Their suppression is crucial for the induction of tolerance. Only cells that react with a given organ, e.g. a transplant or a target of an autoimmune disease, should be removed. As different types of cells express tissue-specific antigens, complete tolerance towards a given tissue is best induced by the tissue itself. This should be true for transplant rejections and also autoimmune diseases. It has long been held that the disease mechanisms underlying autoimmune diseases mimic those seen in transplant rejection. Therefore, it should be possible to adapt strategies that induce specific transplantation tolerance to the treatment of autoimmune diseases. The so-called veto-effect (conventional veto) has been shown to efficiently and specifically tolerize T cells. It functions by expression of the co-receptor CD8 on stimulator cells. Based on this original observation, the approach has been expanded toward the development of hybrid antibodies (hAb) that combine a targeting antibody moiety with the functional region of the CD4 or CD9 accessory molecules. The cells coated with these hAbs inhibited the activation of either CD4+ or CD8+ activation in a highly specific fashion. In the current application, it is proposed to examine the function and activity of the CD8 targeting hAb in animal models of organ transplantation.