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

Tolerance induced by the nondepleting anti-CD4 monoclonal antibody （RIB-512） in the sensitized rats is strongly associated with CD4 y D2+ y D2IL-4 producing Th2-type regulatory T cells。耐受性不是可接受的转移，并且在长期存活的thymectomized受体中被RIL-2轻易破坏，但在永恒的耐受性大鼠中却不存在。由耐受性介导的T细胞的耐受性大鼠或受体的结构学并不影响耐受性的稳定性和转移性，建议新鲜的thymus迁移者是调节性T细胞的细胞来源，Moreover，抗原是必要的，以维持调节性T细胞。被移植的心被切除了两周后，耐受性消失了，但在4周后，耐受性还没有完成，建议克隆能量仍然起作用。在另一方面，两周后，在耐受介导T细胞的能力中切除了被移植的心脏，耐受性没有被破坏，建议用克隆能量来修复受体。下一步，Th 1（IL-2/IFN-g）和Th 2（IL-4/IL 10）细胞因子被比较有竞争力的RT-PCR分析，以打破常规T细胞的动力学。RIP-5/2治疗的受体在移植网站上显示出Th 1和Th 2细胞因子的累积衰退。However，当第二次心脏移植时， IFN-g和IL-10在主移植中被上调，IL-4在第二移植中被上调。However，Th 1和Th 2细胞因子在两个图表中都恢复到较低的水平。从移植站点的细胞因子模式的视点来看，一旦新鲜抗原被移植，沉默的调节T细胞似乎迁移到新的Tx和激活。克隆能量和调节CD 4-YYYYYD 1 + YYYD 1 Th 2-样IL-4生产细胞，将感染耐受性转移到新的试验大鼠受体的队列，贡献到非降解CD 4 mAb （RIB-5/2）诱导在敏感大鼠模型中的永久Tx生存。

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.