Tolerance induction by intrathymic injection of allopeptides.

目的：胸腺内注射供体抗原是实现供体特异性耐受的可能方法之一，但胸腺内注射供体MHC-I类分子多肽的研究尚未见报道。为了分析人类白细胞抗原I类分子在移植物排斥反应中的作用，选择两种不同的人类白细胞抗原I类转基因小鼠进行移植。此外，将其中一种HLAI类基因的多肽注入另一种HLAI类转基因小鼠胸腺内，以研究其诱导特异性耐受的可能性。方法：将一只HLAB35转基因小鼠的皮肤移植物(HLAB35^*01基因转染C3H/He)移植到HLAB51转基因小鼠(HLAB51TGM)上，其中HLAB51^*01基因转染C3H/He。将代表人类白细胞抗原-B35基因多态损伤全序列的7种23-25位合成肽注入小鼠胸腺，胸腺内注射2天后，给小鼠胸腺注射…。移植的M型心脏较多。心脏移植物的排斥反应通过触诊和组织病理学检查来判断。结果：HLAB35TGM的皮肤移植到HLAB51TGM的皮肤移植排斥反应为12.6(SY+-)。[)4.2天(平均(]正数+-[SD]移植后。用CML法检测特异性细胞毒作用，当反应细胞被皮肤移植启动时，这种效应显著。移植到人类白细胞抗原-B51TGM的心脏移植排斥反应发生在22.8(SY+-)。结论：1.HL A-B51TGM主要通过细胞机制排斥皮肤和心脏移植物，这些小鼠可用于研究人类白细胞抗原I类分子在移植物排斥反应中的作用。2.胸腺内注射供体人类白细胞抗原I类分子衍生的多肽，可诱导供体特异性耐受。较少

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