| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
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.
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