The immune response in FVIII^null mice that were preconditioned with a nonmyeloablative regimen, allowing an 8-week recovery before transfusion of platelet-FVIII or low-dose rhF8. FVIII^null mice were preconditioned with 660-cGy TBI. Eight weeks later, animals were transfused with 2bF8^Tg platelets or low-dose rhF8 (2 U/kg). After 8 doses of infusion with either 2bF8^Tg platelets or low-dose rhF8, animals were further challenged with full-dose rhF8 immunization. The anti-FVIII inhibitor titers from different time points were determined by Bethesda assay. (A) Schematic diagram of transfusion in FVIII^null mice that were preconditioned with 660-cGy TBI followed by 8 weeks of recovery. The transgenic platelets were transfused to a level between 25% and 40% of total platelets upon infusion. (B) The inhibitor titers in the animals that received 2bF8^Tg platelet infusion. (C) The inhibitor titers in animals that received low-dose rhF8 infusion. (D) Comparison of inhibitor titers among 6 groups of animals under various conditions. (E) Comparison of total anti-FVIII IgG titers among 6 groups of animals under various conditions. These results suggest that the immune suppression induced by 2bF8^Tg platelet or low-dose rhF8 transfusion occurs during the early phase of BM recovery following 660-cGy TBI.