权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

MECHANISM FOR INDUCTION AND MAINTENANCE OF IMMUNOLOGICAL TOLERANCE IN THE ORGAN TRANSPLANTATION TO THE SENSITIZED RATS

致敏大鼠器官移植免疫耐受的诱导和维持机制

基本信息

批准号：
10671089
负责人：
ONODERA Kazuhiko
金额：
$ 1.79万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671089/
关键词：
IMMUNOLOGICAL TOLERANCE SENSITIZED RAT ANTI-CD4 MONOCLONAL ANTIBODY REGULATORY T CELL THYMUS ANTIGEN DEPENDENCY CLONAL ANGERGY 抗CD4モノクローナル抗体

项目摘要

Tolerance induced by the nondepleting anti-CD4 monoclonal antibody (RIB-512) in the sensitized rats is strongly associated with CD4ィイD2+ィエD2IL-4 producing Th2-type regulatory T cells. Tolerance was not adoptively transferable and was easily broken by rIL-2 in the long-term surviving thymectomized recipients, but not in euthymic tolerant rats. Thymectomy of tolerant rats or recipients of tolerance-mediating T cells did not influence the stability and transferability of tolerance, suggesting that fresh thymus emigrants are the cellular source of regulatory T cells.Moreover, antigen is necessary to maintain regulatory T cells. Two weeks after the removal of the grafted heart, transferability of tolerance disappeared, but tolerance did not until 4 weeks after that, suggesting that clonal anergy was still working. On the other hand, two weeks after the removal of the grafted heart in there cipients of tolerance-mediating T cells, tolerance was not broken, suggesting that the recipient was endowed with clonal anergy.Next, intragraft expression of both Th1 (IL-2/IFN-g) and Th2 (IL-4/IL10) cytokines was examined by competitive RT-PCR to dissect the dynamics of regulatory T cells. Long-term grafts in RIB-5/2 treated recipients showed profound depression of Th1 and Th2 cytokines at the graft site. However, when second cardiac graft was transplanted, IFN-g and IL-10 were up-regulated in the primary grafts, and up-regulation of IL-4 was seen in second grafts. However, Th1 and Th2 cytokines returned to the low level in time in both grafts. From the view point of the cytokine pattern at graft sites, once fresh antigen is transplanted, silent regulatory T cells seems to migrate to new Tx and activate.Clonal anergy and regulatory CD4ィイD1+ィエD1Th2-like IL-4 producing cells, which transfer infectious tolerance to new cohorts of test rat recipients, contribute to non-depleting CD4 mAb (RIB-5/2) induced permanent Tx survival in sensitized rat model.

非消耗性抗CD 4单克隆抗体（RIB-512）诱导的致敏大鼠免疫耐受与产生CD 4 + CD 4 + D2+ IL-4的Th 2型调节性T细胞密切相关。在长期存活的胸腺切除受体中，耐受性不能过继转移，并且很容易被rIL-2打破，但在正常胸腺耐受大鼠中则不然。对耐受大鼠或耐受介导T细胞受体切除胸腺，均不影响耐受的稳定性和可转移性，提示新鲜胸腺移出物是调节性T细胞的细胞来源，而且抗原是维持调节性T细胞所必需的。移植心脏摘除后2周，移植心脏耐受的传递性消失，但移植心脏摘除后4周，移植心脏耐受仍有传递性，表明克隆性无能仍在发挥作用。另一方面，在移植心脏的三个耐受介导的T细胞的受体中，两周后去除移植心脏，耐受没有被打破，这表明受体被赋予克隆性无能。RIB-5/2治疗的受体中的长期移植物显示移植部位的Th 1和Th 2细胞因子的显著抑制。然而，当移植第二心脏移植物时，IFN-g和IL-10在第一移植物中上调，并且IL-4在第二移植物中上调。然而，Th 1和Th 2细胞因子在两种移植物中及时恢复到低水平。从移植部位的细胞因子模式的角度来看，一旦移植新鲜抗原，沉默的调节性T细胞似乎迁移到新的Tx和activated.Clonal无能和调节性CD 4单克隆抗体D1+ CD 4 D1 Th 2-样IL-4产生细胞，转移感染性耐受到新的队列的测试大鼠受体，有助于非耗尽CD 4单克隆抗体（RIB-5/2）诱导的永久性Tx生存在致敏大鼠模型。