Analyzes on artifical induction of antigen-specific immunological tolerance

1.成功地建立了抗小鼠CD48(CD2配体)、CD80(B7-1)、CD86(B7-2)、CD29(整合素β1)、CD49a(整合素α1)、CD49b(α2)、CD49e(α5)、CD49f(α6)、CD40、CD40配体、CD95配体、大鼠CD86、人CD86、CD95、CD95配体的单抗。应用抗LFA-1/ICAM-1、抗VLA-4/VCAM-1、抗CD2/CD48或抗CD80/CD86单抗可诱导心脏、肠或胰岛移植耐受。抗LFA-1/ICAM-1诱导的心脏移植耐受主要由同种异体I类反应性CD8T细胞失活介导，而抗CD2/CD48或抗CD80/CD86诱导的耐受主要由Th2偏离和/或Th1失活介导。这表明不同的机制是造成同种异体移植耐受的原因。应用抗CD80/CD86单抗可预防骨髓移植后致死性移植物抗宿主病。给予抗LFA-1/ICAM-1单抗不仅可以预防大鼠或小鼠的胶原性关节炎，而且可以诱导对相同抗原的后续攻击的抵抗。在发病前短期给予抗LFA-1/ICAM-1单抗可持续预防NOD小鼠糖尿病的发生。注射抗CD80/CD86单抗可预防(NZB×NZW)F1小鼠自身抗体的产生和肾脏疾病。应用抗IL-12单抗不仅可以预防IRBP诱导的B10小鼠实验性自身免疫性葡萄膜视网膜炎(EAU)。IL-12p40(IL-12拮抗剂)基因的导入抑制了同种异体成肌细胞的排斥反应，IL-12p40基因和β-半乳糖基因的导入抑制了β-半乳糖特异性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.