Analyzes on artifical induction of antigen-specific immunological tolerance

1. 我们成功地建立了针对小鼠CD48 （CD2配体）、CD80 （B7-1）、CD86 （B7-2）、CD29（整合素β 1）、CD49a（整合素α 1）、CD49b （α 2）、CD49e （α 5）、CD49f （α 6）、CD40、CD40配体、CD95配体的单克隆抗体，以及针对大鼠CD86、人CD86、CD95、CD95配体的单克隆抗体。给药抗lfa -1/ICAM-1、抗vla4 /VCAM-1、抗cd2 /CD48或抗cd80 /CD86单克隆抗体可诱导心脏、肠或胰岛异体移植耐受。抗lfa -1/ICAM-1处理诱导的心脏移植耐受主要是由同种异体i类反应性CD8 + T细胞失活介导的，而抗cd2 /CD48或抗cd80 /CD86诱导的心脏移植耐受主要是由Th2偏差和/或Th1失活介导的。这表明同种异体移植物耐受的机制是不同的。骨髓移植后致死性GVHD可通过抗cd80 /CD86单克隆抗体预防。抗lfa -1/ICAM-1单克隆抗体不仅可以预防小鼠或大鼠胶原诱导的关节炎，而且还可以诱导小鼠抵抗同一抗原的后续攻击。在胰岛素发作前短期给予抗lfa -1/ICAM-1单抗可持续预防NOD小鼠糖尿病的发生。在（NZB x NZW） F1小鼠中，给药抗cd80 /CD86单克隆抗体可预防自身抗体的产生和肾脏疾病。抗il -12单抗不仅可以预防B10中IRBP引起的实验性自身免疫性葡萄膜视网膜炎（EAU）。但也诱导小鼠抵抗随后的IRBP攻击。IL-12p40 （IL-12拮抗剂）基因的引入抑制同种异体成肌细胞的排斥反应。IL-12p40基因和β -gal基因的引入抑制了β -gal特异性CTL的产生。

1. We succeeded to establish monoclonal antibodies against mouse CD48 (CD2 ligand), CD80 (B7-1), CD86 (B7-2), CD29 (integrin beta1), CD49a (integrin alpha1), CD49b (alpha2), CD49e (alpha5), CD49f (alpha6), CD40, CD40 ligand, CD95 ligand, that against rat CD86, and those against human CD86, CD95, and CD95 ligand.2. Administration of anti-LFA-1/ICAM-1, anti-VLA-4/VCAM-1, anti-CD2/CD48, or anti-CD80/CD86 mAbs could induce cardiac, bowel, or plancreatic islet allograft tolerance.3. The cardiac allograft tolerance induced by the anti-LFA-1/ICAM-1 treatment was mainly mediated by the inactivation of allogeneic class I-reactive CD8^+ T cells, whereas that induced by anti-CD2/CD48 or anti-CD80/CD86 was mediated by Th2 deviation and/or Th1 inactivation. This suggests divergent mechanisms are responsible for allograft tolerance.4. Lethal GVHD after bone marrow transplantation was prevented by the administration of anti-CD80/CD86 mAbs.5. Administration of anti-LFA-1/ICAM-1 mAbs not only prevented mouse or rat collagen-induced arthritis but also induced resistancy against the subsequent challenge with the same antigen.6. Short-term administration of anti-LFA-1/ICAM-1 mAbs before the onset of insulitis persistently prevented the occurrence of diabetes in NOD mice.7. Administration of anti-CD80/CD86 mAbs prevented the autoantibody production and renal disease in (NZB x NZW) F1 mice.8. Administration of anti-IL-12 mAb not only prevented the experimental autoimmune uveoretinitis (EAU) elicited by IRBP in B10. A mice but also induced resistancy against the subsequent challenge with IRBP.Introduction of IL-12p40 (IL-12 antagonist) gene inhibited the rejection of allogeneic myoblasts.Introduction of IL-12p40 gene along with beta-gal gene inhibited the generation of beta-gal-specific CTL.