Application of antisense-peptides associated with immunological rection in organ transplantation

免疫反应相关反义肽在器官移植中的应用

基本信息

批准号：
11557083
负责人：
YOKOYAMA Itsuo
金额：
$ 8.64万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

In allograft transplantation, interaction between lymphocytes and antigen presenting cells is a key event followed by various types of immunological response. The antigen presenting cell from the graft also plays an important role in the initial response leading to an augmented rejection response of the graft. In recent years, such donor graft-derived antigen presenting cells are considered to remain for a considerable length of time in the host remote from the graft site that is observed particularly in the long-term survivors. This has led to the concept of its significance in relation to a microchimerism. In the present research, we have focused on the role of peptides of the immunologically responsive proteins, particularly those associated with donor-derived antigen presenting cells. The following are the main aims of the present study in the investigation for : 1) clarification of molecular-biological mechanism in the induction of immunological tolerance in the allograft transplantation ; 2) insights for cell surface proteins and intra-cellular substances and their signal transduction ; 3) analysis of antisense peptides responsive for immunological tolerance ; 4) preclinical study for induction of tolerance.Immunologically responsive proteins can contain portions of peptides which determine the bioactivity that are usually consisted of a limited length of peptides, a good example of which is a Fas antigen and ligand protein. The results of the present study indicate that a better immunological regulation than a conventional method can be achieved by focusing on the interaction of the bioactive proteins between the immunologically responsive cells in the organ transplantation,

在同种异体移植中，淋巴细胞和抗原呈递细胞之间的相互作用是随后发生各种类型的免疫反应的关键事件。来自移植物的抗原呈递细胞在导致移植物排斥反应增强的初始反应中也发挥着重要作用。近年来，这种供体移植物衍生的抗原呈递细胞被认为在远离移植部位的宿主中保留相当长的时间，这在长期存活者中尤其观察到。这导致了其与微嵌合体相关的重要性的概念。在本研究中，我们重点关注免疫反应蛋白肽的作用，特别是与供体来源的抗原呈递细胞相关的肽。本研究的主要研究目的如下：1）阐明同种异体移植中诱导免疫耐受的分子生物学机制； 2）深入了解细胞表面蛋白和细胞内物质及其信号转导； 3) 分析对免疫耐受敏感的反义肽； 4)诱导耐受的临床前研究。免疫反应蛋白可以含有决定生物活性的肽部分，这些肽通常由有限长度的肽组成，一个很好的例子是Fas抗原和配体蛋白。本研究的结果表明，通过关注器官移植中免疫应答细胞之间生物活性蛋白的相互作用，可以实现比常规方法更好的免疫调节。