The role of splenectomy in a non-lethal preparative regimen for induction of tolerance in non-human primates

214 [Introduction] Multilineage chimerism and long term acceptance of renal or cardiac allografts has been produced in non-human primates conditioned with pretransplant total body irradiation (TBI), thymic irradiation (TI) and ATG; splenectomy and DBM on the day of organ transplantation; and a 4-week post transplant course of cyclosporine (CYA). Previous studies demonstrated that removal of either DBM, TBI or CYA from the regimen resulted in allograft rejection within 2-8 weeks. The current studies were undertaken to evaluate the role of splenectomy in the protocol. [Method] Four renal allograft recipients received the entire conditioning regimen except for splenectomy. Another six recipients received the full protocol with (n=3) or without (n=3) splenectomy but renal allograft placement was delayed until 4 months later. [Results] In contrast to our previous observations of no alloantibody production and long term (>190days) organ allograft survival in 82% of recipients conditioned with the full regimen (Group A), monkeys conditioned without splenectomy rejected their allografts by day 117 and anti-donor antibody was detected in two of two recipients tested (Group B). In the six monkeys treated with delayed kidney transplantation until 4 months, three recipients without splenectomy (Group C) developed anti-donor antibody and rejected kidney allografts immediately after transplantation (0, 7, 12 days). None of three monkeys with splenectomy (Group D) developed anti-donor antibody. TableTable[Conclusion] In our current regimen, splenectomy appears to be essential for long term allograft survival. The development of donor specific alloantibody in all non-splenectomized recipients tested suggests inadequate control of B cell responses prevents induction of allograft tolerance in these animals.