Tolerance induction by intrathymic injection of allopeptides.

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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