Immune Suppression Produced by Intrathymic Inoculation With Xenogeneic Antigen and Whole-Body γ-Irradiation in a Pig-to-Monkey Heart Transplantation Model

Abstract

Objective To validate the use of pig-to-monkey transplantation as an experimental animal model for study of the induction of immune suppression of cardiac xenografts via intrathymic inoculation with xenogeneic spleen cells and whole-body γ-irradiation. Materials and Methods Donors (Meishan pigs) and recipients (Rhesus monkeys) were randomized into 3 groups. Group 2 was the control group; group 2 received whole-body irradiation, and group 3 received whole-body irradiation and intrathymic inoculation. In each group, survival time of heterotopic heart xenografts in monkeys were observed. A mixed lymphocyte reaction assay with 3H thymidine was used to examine changes in lymphocyte function in all groups on the day of transplantation. In each group, recipient serum was harvested for analysis of IL-2 and IL-10 concentrations. Results Mean (SD) survival time of donor hearts in group 3 was significantly longer (91.1 [22.8] hours) than in group 1 (36.6 [5.8] hours) ( P < .01). The results of mixed lymphocyte reaction assay demonstrated a significant reduction in the stimulation index in group 3 compared with groups 1 and 2 ( P < .01) when recipient splenocytes responded to the donor stimulator. The IL-2 concentration in recipients in all groups was much higher during rejection of xenografts than before transplantation ( P < .01). Conclusion These results suggest that pretreatment with intrathymic inoculation or whole-body irradiation induces T-cell immunosuppression. The IL-2 concentration is closely correlated with xenograft rejection.