Anti-CD3 prevents anti-FVIII Ab formation in BALB/c hemophilia A mice. (A) In 4 separate experiments using the optimized dose of anti-CD3 (10 μg/day for 5 days), the incidence of FVIII inhibitor formation was determined in HBSS-treated mice (n = 30) and anti-CD3–treated mice (n = 33). The incidence of FVIII inhibitor formation shown was determined 1 week after the final FVIII immunization. Data are mean plus or minus SD. (B) The FVIII inhibitor titer in Bethesda units per milliliter in the mice from panel A is shown at 1 week after the final FVIII immunization. (C) The anti-FVIII Ab isotypes were analyzed in the plasma of “protected” anti-CD3–treated (n = 5) (anti-CD3–treated mice that did not form inhibitors after 4 FVIII immunizations) and HBSS-treated mice (n = 8) 3 weeks after the final FVIII immunization. Data are mean plus or minus SEM. (D) The effect of anti-CD3 at 10 μg/day for 5 days (the optimized dose) on T-cell populations in hemophilia A BALB/c mice (n = 5) is shown at 3 days after the final anti-CD3 injection and is compared with untreated and age-matched animals (n = 5).