Rabbit-antithymocyte globulin (rATG) is commonly used in solid organ transplantation to prevent and treat allograft rejection. Also, immunosuppressive drug is used for graft to permit long-term survival in animal transplantation model. Although rATG is also commonly used in non-human primates, the optimal dose has not been reported. In this study, we evaluated which cumulative dose of rATG was most appropriate for transplantation in non-human primate, compared to clinical cases.
In this study, cynomolgus monkeys were treated with 5 mg/kg of rATG (Thymoglobulin®, Genzyme Ltd., UK) intravenously twice (totally 10 mg/kg, n=2) or 4 times (totally 20mg/kg, n=4). Their peripheral blood were collected and analyzed by flow cytometry. Also their subpopulation of T cells like effector memory cells, central memory cell and naïve T cells were analyzed serially. And, to assess the effect of T-cell depletion in lymphoid organ, their lymph node and spleen were also collected and analyzed by immunohistochemistry at the indicated time points.
The absolute number of lymphocytes were decreased rapidly at day 1 and then maintained for 2 weeks in 20mg/kg rATG group but not maintained in 10 mg/kg rATG group. Experimental data of lymphoid tissues demonstrate that rATG monotherapy with 20mg/kg affects T cell-depletion, especially in spleen, although Lymph node was weakly affected by rATG induction. During the early period of rATG treatment, the pattern of changes in T cell subpopulation in 20mg/kg group showed similar with that in kidney transplant patients treated with ATG (totally 4.5 mg/kg). Therefore, we performed kidney transplantation in non-human primate with 20 mg/kg rATG induction and compared these to the results of a human KT.
These data show that lymphocyte-depletion induced by rATG was influenced by the cumulative dose, and show that an rATG dose of 20 mg/kg is suitable for induction therapy for renal transplantation in the cynomolgus monkey when compared to human kidney transplantation.
2Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul , Korea
1Department of Surgery, Samsung Medical Center,Sungkyunkwan University School of Medicine, Seoul , Korea