The Study Of Inducing Cardiac Allografts Immune Tolerance By Intrathymic Inoculating Allogeneic Spleen Cells And Whole-BodyγRadiation In The Pig

Heart transplantation has become a therapeutic option for patients with end-stage heart disease. Advances in immunosuppressive drug have yielded improvement of transplantation, yet long-term survival recipient complications and graft loss continue to accompany chronic immunosuppression. Induction of tolerance may hold the key to improving transplant longevity and quality of life in recipient and increase the cost- effectiveness of transplant therapy at the same time. Intrathymic inoculating allogeneic spleen cell is one of the most effective approaches of inducing tolerance.Our study apply this approach to investigate wheather it can induce immune tolerance in the pig. Purpose: Validation of the pig as an experimental animal model for the study on inducing the immune tolerance to cardiac allografts by intrathymic inoculation with allogeneic spleen cells and whole-body ~ - radiation. Material and Methods: The experimental animals were divided into 3 groups.In group I (blank group), without IT and WBI,HCT were performed in recipient pigs. In group 2 (WBI group) and group 3 (IT&WBI group), the evolution of the lymphocyte and its subsets CD4, CD8 count was followed for up to 14 days after irradiation in pigs exposed to whole-body? v -radiation at dose 2 Gy. In group 3,synchronously, allogeneic spleen cell was injected into the thymus of the recipient pig. The mixed lymphocyte culture was applied before intrathyrnic inoculation and after one week and two weeks of intrathvmie inoculation.Then heterotopic cardiac transplant was performed in pigs of group 2 and 3 after 2 weeks of pretreatment. Survival time of cardiac allografts were determined by palpation of donor Ill y heart beat in the abdomen .In each group ,recipient semm was harvested in order to analyze IL-2 and IL-i O,at various periods including pretransplant,ld,2d, 3d and 5d after transplant. Results: Compared with the pre-irradiation levels, the count of lymphocyte and its subsets CD4,CD8 was significantly decreased after irradiation, especially CD4 T cell. The results of MLR showed that the stimulative effect after 2 weeks of intrathymic inoculation was a notable decrease comparing with the pre-intrathymic inoculation, 1 week after intrathymic inoculation and that in group2(P