The Immune Effect Of Intrathymic Inoculation And Whole Body Irradiation On Production Of Antibody In Pig-to-monkey Heart Transplantation

Introduction: The inadequate supply of human organs has created a strong interest in the use of non-primate organs for clinical transplantation, but vigorous immune reactions prevent those from current use in humans. The expression of transgenic human complement regulatory genes confers to porcine organs resistance to complement-mediated hyperacute rejection[1][2][3][4]. However, significant immune responses directed against the xenograft, and the xenografts are eventually rejected by a process collectively referred to as acute humoral xenograft rejection(AHXR) or delayed xenograft rejection(DXR). The production of Elicited Xenorecative Antibody(EXA) is a dominant feature of AHXR/DXR and there is increasing evidence that EXA are the primary mediators of AHXR/DXR[5][6].This study was designed to investigate the immune effect of intrathymic inoculation and whole body irradiation on production of monkey anti-pig xenoantibody in pig-to-monkey model.Materials and methods: In this experiment, Meishan-pig and Rhesus monkey were, respectively, selected as donor and recipient. Donor(Meishan-pig) and recipient(Rhesus monkey) were divided randomly into three groups: The control group(Group A), WBI group(Group B), irradiation and intrathymic injection group(Group C).The change of antibody(IgM and IgG) after pretreatment and xenotransplantation were detected by the flow cytometry. Results: The level of natural antibody IgM was obviously dropped after the whole body irradiation of 2.5 Gy 60Co Y -radial (p<0.01), but the level of natural antibody IgG was not clearly changed (p>0.05). The level of natural antibody IgM and IgG was no obvious difference between Group C and the Group B (p>0.05). Mean survival time of donor heart was 36.2 5.9 hours in Group A, 65.2 6.6 hours in Group B and 91.5 23.1 hours in Group C. The survival time in Group B and Group C were significantly longer than that in Group A (p<0.01), and that was significantly longer than in Group C(p<0.05). After pig-to-monkey heart xenotransplantation, the level of elicited xenorecative antibody(EXA) IgM and IgG in the group C was ascended slowlier than that in group A and group B (p<0.01).conclusions: WBI (2.5 Gy) could decrease the level of natural antibody IgM and benefit to prolong the survival time of the donor heart. In the Acute Humoral Xenograft Rejection (AHXR), the Elicited Xenorecative Antibody (EXA) played a primary role, and had an intimate correlation with the rejection of the heart graft. The Elicited Xenorecative Antibody IgG that was activated largely was the primary mediators of the Acute Humoral Xenograft Rejection. At the same time, we found that the Elicited Xenorecative Antibody IgM performed an important function in the Acute Humoral Xenograft Rejection, and that the raise of the level of the Elicited Xenorecative Antibody IgM accelerated the rejection of the graft. The thymus had an important effect on the production of elicited xenorecative antibody. Therefore irradiation and intrathymic injection could restrain the production of elicited xenorecative antibody IgM and IgG in pig-to-monkey model, and prolonged the survival time of the graft.