The immunogenicity of platelets that contain FVIII in naïve FVIII^null mice. Platelets isolated from transgenic mice (2bF8^Tg), in which FVIII expression was driven by the platelet-specific αIIb promoter, were infused into FVIII^null mice without any preconditioning. The transgenic platelets were transfused to a level between 18% and 56% of total platelets upon infusion. (A) Schematic diagram of platelet transfusion in naïve FVIII^null mice. (B) Tail-clipping test on FVIII^null mice after transfusion of 2bF8^Tg platelets. Tail-clipping test was performed 1 day after platelet infusion to assess phenotypic correction of FVIII^null coagulation defect. (C) The levels of platelet-FVIII in transfused recipients. Platelets were collected 1 week after platelet infusion, and functional FVIII activity levels were determined by a chromogenic assay on platelet lysates. (D) The inhibitor titers in recipients after infusion of 2bF8^Tg platelets or rhF8. The anti-FVIII inhibitor titers were determined by Bethesda assay. (E) The total anti-FVIII immunoglobulin (Ig) G titers in recipients after infusion of 2bF8^Tg platelets or rhF8. The total anti-FVIII IgG titers were determined by ELISA assay. These results demonstrate that transfusion of platelets containing FVIII into naïve FVIII^null mice neither elicits an anti-FVIII immune response nor induces immune suppression. FD, full dose; Wks, weeks.