The Effect Of Intrathymic Inoculation To Delayed Xenograft Rejection With Different Xenogeneic Antigens

Objective This study was designed to investigate the effect of intrathymic inoculation with xenogeneic antigens and whole body irradiation on the delayed xenograft rejection (DXR) in the model of mouse to rat heart xenotransplantation, to inquire the effect of T lymphocytes in delayed xenograft rejection and the impression of function of vascular endothelial system with intrathymic inoculation.Materials and methods Donor(masculine NIH mouse) and recipient (masculine SD rat) were divided randomly into four groups. Group A (Control group):without pretreatment; Group B (WBI group):the recipients received 3.5Gy Co~60 γ-ray whole body irradiation(WBI) 17 days before transplantation; Group C (WBI plus intrathymic inoculation with mouse SCs group): after WBI, the recipient thymus was injected with the mouse SCs(spleen cells) 5×10~6 3days later ,and Group D (WBI plus intrathymic inoculation with the mouse VECs group):after WBI, the recipient thymus was injected with the mouse VECs(vascular endothelial cells) 5×10~6 3days later. After different pretreatments to the recipients, the abdominal heterotopic heart transplantation from mouse to rat were performed. The grafted heart mean survival time (MST), the results of MCR (mixed cell reaction) before transplantation were observed. The change of antibody IgG of the recipient before and after transplantation was detected by the flow cytometry(FCM).The change of VCAM-1 and ICAM-1 of the recipient after transplantation was detected by ELISA.Results(1)MST: Group D (156.2±19.7h)>Group C (125.6±18.2h) >Group B (94.4±21.5h)>Group A (59.9±4.7h). Group D and Group C were prolonged significantly (P<0.05), and Group D was longer than Group C (P<0.05).(2)The resultsof MCR: The proliferation of the recipient T cells in Group D and Group C was particularly inhibited (P<0.05). There was difference between Group D and Group C (P<0.05). ?The change of antibody IgG of the recipient: The level of IgG in Group D and Group C ascended slower significantly after transplantation (P<0.05). There was difference between Group D and Group C (PO.05). ?The change of VCAM-1 and ICAM-1 of the recipient: The level of VCAM-1 and ICAM-1 in Group D and Group C ascended slower significantly after transplantation (PO.05). There was difference between Group D and Group C (P<0.05). (5) Pathology:All Group xenograft heart show the pathology of the delayed xenograft rejection.Conclusion ? Intrathymic inoculation with different xenogeneic can inhibit proliferation of recipiential T lymphocytes, inhibit the entrain of elicited xenorecative antibody, delay DXR process and can prolong survival time of the grafted heart, but can't overcome DXR completely in the heart xenotransplantation of mouse to rat. (2) Intrathymic inculation with donor VECs can reduce activation of donor vascular endothelial cell, and it was the better inducer than donor SCs in the heart xenotransplantation. ?The expression of ICAM-1 and VCAM-1 was compact persistence with the genesis and development of DXR. It could be considered an investigated factor in the treatment of organ transplantation and exploit a new direction in immune rejection of xenotransplantation.