INDUCTION OF SPECIFIC IMMUNE TOLERANCE

描述：（改编自研究者摘要）：免疫系统是 负责对抗疾病的主要生物防御系统。然而，在这方面， 免疫反应也可能是有害的。在移植的情况下， 虽然免疫系统反应适当，但它仍然会造成伤害， 破坏移植的器官在自身免疫性疾病中，免疫系统 会攻击自身并攻击其他正常组织在这两种情况下， 重要的是暂停免疫系统的破坏性功能， 维持正常的免疫反应。目前，在临床情况下， 一般的免疫抑制被诱导，病人的防御， 传染病的挑战受到削弱。目前正在寻求战略， 成功诱导特异性无反应性（耐受性）而不影响 正常的免疫功能。 免疫系统的重要细胞是T细胞。它们控制着许多免疫系统 反应，并作为效应细胞。对它们的抑制对于 诱导耐受性。只有与给定器官反应的细胞，例如 移植物或自身免疫性疾病的目标，应该被移除。作为 不同类型的细胞表达组织特异性抗原，完全耐受 最好由组织本身诱导。这应该是 移植排斥和自身免疫性疾病也是如此。人们早就 认为自身免疫性疾病的发病机制类似于 在移植排斥反应中可见。因此，应该能够适应 诱导特异性移植耐受治疗的策略 自身免疫性疾病 所谓的否决效果（常规否决）已被证明是有效的， 特异性耐受T细胞。它通过表达辅助受体发挥作用 CD8刺激细胞。根据这一原始观察，该方法 已经扩展到开发杂交抗体（hAb），其结合联合收割机a 具有CD4或CD9功能区的靶向抗体部分 辅助分子用这些hAbs包被的细胞抑制了活化 CD4+或CD8+的活化。在当前 应用中，建议检查CD8的功能和活性， 在器官移植动物模型中靶向hAb。

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.