Establishment of producing immunologic tolerance by intrathymic antigen inoculation

我们将重点放在狗和猪对猪作为供体来源的免疫反应上。此外，我们还试图通过胸腺内注射来检测产生耐受的可能性。未经修饰的犬血清可获得近100%的PK15细胞。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、半乳糖苷和N-乙酰-β-D-氨基葡萄糖)对犬血清的细胞损伤有抑制作用(分别为47.4%、45.2%、34.8%、25.0%、23.1%)。两者混合使用，显示出保护作用(76.5%)。与PK15细胞和WGA凝集素结合，可抑制PK15细胞的损伤。本研究提供的证据表明：(1)PK15细胞上有一些碳水化合物可能是抗犬抗猪抗体的靶标；(2)作为抗原的碳水化合物可能具有抑制作为抗原的犬抗猪抗体结合的有用作用，以防止超急性排斥反应。将NIH小型猪注射到胸腺(胸腺组…多P)或有胰岛的脾(脾组)。在胸腺组：1)混合淋巴细胞反应(MLR)的抗供体刺激指数(SI)降低，并保持在较低水平；2)细胞介导的淋巴细胞毒(CML)试验中，外周血淋巴细胞(PBL)显示最低的细胞毒活性；3)MLR-CML中的抗供体细胞毒性T淋巴细胞(CTL)活性消失；4)增殖T淋巴细胞(PTL-p)前体细胞(PTL-p)对供体LC的反应降至检测不到的水平；5)未检测到抗供体细胞毒抗体；与之相反，在1月龄的脾脏组：1)MLR的抗供体SI升高；2)CML和MLC-CML的抗供体细胞毒作用增强；3)抗供体LC的PTL-p增加；4)从1周开始检测到抗供体抗体。这些结果表明，胸腺内接种胰岛可以诱导PBL的无反应性和对全身性抗供体细胞毒抗体的抑制，并维持对供体的稳定无反应性，而不是针对第三方抗原。较少

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