Analyses on artifical induction of antigen-specific immunological tolerance
Analyses on artifical induction of antigen-specific immunological tolerance
批准号:
08457109
负责人:
YAGITA Hideo
金额:
$5.06万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
1996
资助国家:
日本
项目状态:
已结题
起止时间:
1996 至 1998
中文摘要
1、抗lfa -1 /ICAM-1诱导的心脏移植耐受主要是由同种异体分类反应性CD8 + T细胞失活介导的,而抗cd /fCD48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。2、抗lfa -1 / icam -1或抗cd8oicd86治疗诱导的心脏异体移植物耐受性非常稳定,不会被随后转染了IL-2、IL-12或cd80基因的供体型细胞的攻击所破坏。3、骨髓移植后致死性GVHD可通过抗cdbo /CD86单抗预防。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。抗il -12单抗不仅可以预防IRBP在BlO中引起的实验性自身免疫性葡萄膜视网膜炎(EAU)。在随后的irbp攻击中,小鼠也被诱导对…产生抗性。l -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。我们通过生成单克隆抗体来表征人和小鼠FasL的表达和功能。在致死性急性GVHD小鼠模型中,给予抗fasl和抗tnfalpha单克隆抗体可导致嵌合耐受状态。9、我们发现,FsaIFasL系统介导了异基因肝细胞的cd80 / cd86非依赖性排斥反应。我们发现FasL在角膜内皮上的表达对异体角膜移植的存活起着至关重要的作用。当fasl转染的细胞被中性粒细胞快速排斥时,IL-b或tgf - β的共同转染抑制了中性粒细胞介导的排斥反应。我们建立了针对小鼠cd70、OX4OL、CD3OL和4-1BBL的单克隆抗体,并表征了这些共刺激分子的表达和功能。13、我们建立了针对大鼠cd80、CD86和OX4OL的单抗,并表征了这些共刺激分子的表达和功能。少
英文摘要
1, The cardiac allograft tolerance induced by the anti-LFA-l/ICAM-1 treatment was mainly mediated by the inactivation of allogeneic classi-reactive CD8^+ T cells, whereas that induced by anti-CD/fCD48 or anti-CD8O/CD86 was mediated by Th2 deviation and/or Th1 inactivation. This suggests divergent mechanisms are responsible for allograft tolerance.2, The cardiac allograft tolerance induced by the anti-LFA-l/ICAM-l or anti-CD8OICD86 treatment was so stable that it could not be broken by subsequent challenge with donor-type cells transduced with IL-2, IL-12, or CD8O genes.3, Lethal GVHD after bone marrow transplantation was prevented by the administration of anti-CDBO/CD86 mAbs.4, Short-term administration of anti-LFA-1/ICAM-l mAbs before the onset of insulitis persistently prevented the occurrence of diabetes in NOD mice.5. Administration of anti-IL-12 mAb not only prevented the experimental autoimmune uveoretinitis (EAU) elicited by IRBP in BlO.A mice but also induced resistancy against … More the subsequent challenge with IRBP.6. Introduction of LL-12p40 (IL-12 antagonist) gene inhibited the rejection of allogeneic myoblasts.7. We characterized the expression and function of human and murine FasL by generating mAbs.8, In a murine model of lethal acute GVHD, administration of anti-FasL and anti-TNFalpha mAbs led to a chimeric state of tolerance.9, We revealed that CD8O/CD86-independent rejection of allogeneic hepatocytes is mediated by FsaIFasL system.10, We revealed that FasL expressed on corneal endothelium critically contributes to corneal allograft survival.11, While FasL-transfected cells underwent repid rejection by neutorphils, co-transfection of IL-b or TGF-beta inhibited the neutrophil-mediated rejection.12, We established mAbs against mouse CD7O, OX4OL, CD3OL, and 4-1BBL and characterized the expression and function of these costimulatory molecules.13, We established mAbs against rat CD8O, CD86, and OX4OL and characterized the expression and function of these costimulatory molecules. Less
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Maeda, K., Sato, T., Azuma, M., Yagita, H., and Okumura, K.: "Characterization of rat CD80 and CD86 by molecular cloning and mAb." Int.Immunol.9. 993-1000 (1997)
Maeda, K.、Sato, T.、Azuma, M.、Yagita, H. 和 Okumura, K.:“通过分子克隆和 mAb 表征大鼠 CD80 和 CD86。”
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通讯作者:
Nakano,H.: "Differential regulation of IKKα and IKKβ by two upstream kinases,NIK and MEKK1." Proc.Natl.Acad.Sci.USA. 95. 3537-2542 (1998)
Nakano, H.:“两种上游激酶 NIK 和 MEKK1 对 IKKα 和 IKKβ 的差异调节。Proc.Natl.Acad.Sci.USA 95. 3537-2542 (1998)。
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Oshima,H.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.10. 517-526 (1998)
Oshima,H.:“通过分子克隆和 mAb 表征鼠 CD70。”
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Kato,K.: "Local production of the p40 subunit of interleukin 12 suppresses T-helperl-mediated immune responses and prevents allogeneic myoblast rejection." Proc.Natl.Acad.Sci.USA. 93. 9085-9089 (1996)
Kato,K.:“白细胞介素 12 的 p40 亚基的局部产生可抑制 T-helper1 介导的免疫反应,并防止同种异体成肌细胞排斥。”
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Saito,K.: "Effect of CD80 and CD86 blockade and anti-IL-12 treatment on mouse acute graft-versus-host disease." Eur.J.Immunol.26. 3098-3106 (1996)
Saito,K.:“CD80 和 CD86 阻断以及抗 IL-12 治疗对小鼠急性移植物抗宿主病的影响。”
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共 62 条
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