Tolerance induction by intrathymic injection of allopeptides.

通过胸腺内注射同种肽诱导耐受。

• 批准号: 07807109
• 负责人: ANDO Yuichi
• 金额: $ 1.54万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07807109/
• 关键词: synthetic peptide; MHC class I; transgenic mice; intrathimic injection; heart transplantation; 合成アプチド

PURPOSE : One of possible methods to achieve donor specific tolerance is intrathymic injection of donor antigen, but no report was available about intrathymic injection of peptides of donor MHC class I molecules. In order to analyze the role of HLA class I molecules on graft rejection, two different HLA class I transgenic mice were selected and transplantation was performed. In addition, peptides from one of the HLA class I were injected intrathymically to the other HLA class I transgenic mouse to study the possibility of specific tolerance induction.METHODS : A skin graft from an HLA-B35 transgenic mouse (HLA-B35TGM), in which the HLA-B35^*01 gene is transfected to C3H/He, was transplanted to HLA-B51 transgenic mice (HLA-B51TGM), in which the HLA-B51^*01 gene is transfected to C3H/He. Seven kinds of 23 to 25 mer synthetic peptides, representing full sequences of the polymorphic lesion of HLA-B35, were injected to the thymus of HLA-B51TGM.Two days after intrathymic injection, HLA-B35TG … More M heart was transplanted. Rejection of the heart graft was judged by palpation and histopathological findings. Standard CML assay was performed between the transgenic mice to study the specific cellular cytotoxity.RESULTS : Skin grafts from HLA-B35TGM transplanted to HLA-B51TGM were rejected 12.6 (]SY.+-。[) 4.2 days (mean (]SY.+-。[) SD) after transplantation. Specific cytotoxity was detected by CML assay and this effect was significant when responder cells were primed by skin grafting. Heart grafts from HLA-B35 TGM transplanted into HLA-B51TGM was rejected on 22.8 (]SY.+-。[) 4.2 days after transplantation, whereas mean heart graft survival was more than 60 days when some HLA-B35 peptides were injected intrathymically to HLA-B51TGM prior to heart transplantation.CONCLUSIONS : 1. HLA-B51TGM reject HLA-B35TGM skin and heart graft mainly by cellular mechanism, and these mice are useful to study the role of HLA class I molecules on graft rejection. 2. Intrathymic injection of peptides derivedfrom donor HLA class I molecules has a great chance to induce donor specific tolerance. Less

目得：胸腺内注射供者抗原是获得供者特异性免疫耐受的可能方法之一，但胸腺内注射供者MHC I类分子多肽的研究未见报道。为了分析HLA I类分子在移植排斥反应中的作用，选择了两种不同的HLA I类转基因小鼠并进行移植。另外，将来自其中一种HLA I类的肽注射到另一种HLA I类转基因小鼠的胸腺内，以研究特异性耐受诱导的可能性。HLA-B35转基因小鼠的皮肤移植将其中HLA-B35^*01基因转染至C3 H/He的HLA-B35 TGM移植至HLA-B51转基因小鼠（HLA-B51 TGM），其中HLA-B51^*01基因被转染至C3 H/He。将代表HLA-B_（35）多态性损伤区全序列的7种23 ~ 25聚体合成肽注射到HLA-B_（51）TGM胸腺内，注射后2天，HLA-B_（35）TG ...更多信息 我的心脏被移植了。通过触诊和组织病理学检查判断心脏移植物的排斥反应。结果：HLA-B51 TGM与HLA-B35 TGM的皮肤移植物排斥反应为12.6（± SD）。[）4.2天（平均（）SY. ±.（SD）。CML检测特异性细胞毒性，当反应细胞通过皮肤移植致敏时，这种效应是显著的。HLA-B_（35）TGM移植于HLA-B_（51）TGM的心脏移植物在22.8（±）SY时发生排斥反应。移植后平均存活时间为4.2天，而在心脏移植前胸腺内注射HLA-B51 TGM的HLA-B35肽段，移植心脏平均存活时间超过60天。HLA-B51 TGM主要通过细胞机制对HLA-B35 TGM皮肤和心脏移植物产生排斥反应，为进一步研究HLA-B35 TGM Ⅰ类分子在移植排斥反应中的作用提供了实验动物模型。2.胸腺内注射供者HLA-I类分子衍生肽有很大机会诱导供者特异性免疫耐受。少

项目成果

Beck, Y.: "MHC peptides and tolerance induction" Molecular Medicine. (in press).

Beck, Y.：“MHC 肽和耐受诱导”分子医学。

別宮好文: "MHCペプチドと免疫寛容" Molecular Medicine. (印刷中)34・7. (1997)

别宫义文：“MHC 肽和免疫耐受”《分子医学》（出版中）34・7（1997 年）。

別宮好文: "MHCペプチドと免疫寛容" Molecular Medicine. 34.7(印刷中). (1997)

Yoshifumi Betsumiya：“MHC 肽和免疫耐受”《分子医学》34.7（出版中）。