Establishment of producing immunologic tolerance by intrathymic antigen inoculation

我们重点研究了狗和猪对作为供体来源的猪的免疫反应。此外，我们还尝试了胸腺内注射产生耐受的可能性，未修饰的犬血清引起近100%的PK 15细胞产生耐受。5种碳水化合物（N-乙酰-β-D-甘露糖胺、α-D-半乳糖-1-磷酸、阿拉伯半乳聚糖、半乳糖醛（ICN）和N-乙酰-β-D-葡萄糖胺）对犬血清引起的细胞损伤的抑制率分别为47.4，45.2，34.8，25.0，23.1%。两者混合使用，保护效果达76.5%。WGA凝集素与PK 15细胞联合收割机对PK 15细胞损伤有抑制作用。本研究证明：（1）PK 15细胞表面存在的糖类抗原可能是抗犬抗猪抗体的靶点;（2）抑制糖类抗原与犬抗猪抗体的结合可能对预防超急性排斥反应有一定的作用。 ...更多信息 p）或脾（脾组）与胰岛。在Thirst组中：混合淋巴细胞反应（MLR）的抗供者刺激指数（SI）下降并维持在低水平，外周血淋巴细胞（PBL）在细胞介导的淋巴细胞毒性（CML）试验中显示最低的细胞毒活性，MLR CML中抗供者细胞毒性T淋巴细胞（CTL）活性降至检测不到，4抗供者LC的增殖T淋巴细胞前体（PTL-p）降至检测不到的水平; 5）未检测到抗供体细胞毒性抗体;相反，在脾组中，在1个月时：1）MLR的抗供体SI增加; 2）CML和MLC-CML中的抗供体细胞毒性活性增加; 3）抗供体LC的PTL-p增加; 4）从1周开始可检测到抗供体抗体。这些结果表明，胸腺内接种胰岛诱导PBL的无反应性，以及抑制系统性抗供体细胞毒性抗体，并保持稳定的无反应性针对供体，但不是第三方抗原。少

We have focused on the dog and pig immune responses toward the pig as the donor source. Furthermore, we try to examined the potentialities of the producing tolerance by intrathymic injection.Unmodified canine serum caused approximate 100% PK15 cell. 5 carbohydrates (N-acetyl-β-D-Mannosamine, a -D-Galactose-1-phosphate, Arabinogalactan, Galactal(ICN) and N-acetyl-β-D-Glucosamine) were inhibited the cell damage against canine serum (47.4, 45.2, 34.8, 25.0, 23.1% respectively). And they were mixed, it was showed the protective effect (76.5%). The combine with PK15 cells and WGA lectin was obtained inhibition of PK15 cell damage. This study provides the evidence that (1) there are some carbohydrates on PK15 cells that may be the target against canine anti pig antibodies, (2) there may be useful role for inhibition to binding between carbohydrates as antigen and canine anti pig antibodies in order to prevent hyperacute rejection.NIH minipigs were injected into either the thymus (Thymus grou … More p) or the spleen (Spleen group) with islets. In the Thymus group: 1) Anti-donor stimulation indices (SI) of mixed lymphocyte reactions (MLR) decreased, and remained low; 2) Peripheral blood lymphocytes (PBL) showed minimal cytotoxic activities in cell mediated lymphocytotoxicity (CML) assays; 3) Anti-donor cytotoxic T lymphocyte (CTL) activities in MLR-CML became undetectable; 4) Precursors of proliferating T lymphocytes (PTL-p) against donor LC decreased to an undetectable level; 5) Anti-donor cytotoxic antibodies were not detected; In contrast, in the Spleen group at 1 month: 1) Anti-donor SI of MLR increased; 2) Anti-donor cytotoxic activities increased in both CML and MLC-CML; 3) The PTL-p against donor LC increased; 4)Anti-donor antibodies were detectable starting from 1 week. These results demonstrated that intrathymic inoculation of islets induces unresponsiveness of PBL as well as suppression of systemic anti-donor cytotoxic antibody, and maintenances stable unresponsiveness directed against donor, but not third-party antigens. Less