Inhibitor antibody development and T cell response to human factor VIII in murine hemophilia A

作     者：Qian, JJ Borovok, M Bi, L Kazazian, HH Hoyer, LW 

作者机构：Amer Red Cross Holland Lab Rockville MD 20855 USA George Washington Univ Sch Med & Hlth Sci Dept Med Washington DC 20052 USA Univ Penn Sch Med Dept Genet Philadelphia PA 19104 USA 

出 版 物：《THROMBOSIS AND HAEMOSTASIS》 (Thromb. Haemost.)

年 卷 期：1999年第81卷第2期

页      面：240-244页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：抗体特异性 用药计划表 因子Ⅷ/遗传学 因子Ⅷ/免疫学 因子Ⅷ/治疗应用 血友病A/并发症 血友病A/免疫学 血友病A/治疗 出血/病因学 同种抗体/生物合成 同种抗体/免疫学 淋巴细胞活化 淋巴细胞协同作用 小鼠 近交C57BL 小鼠 基因敲除 脾/细胞学 T淋巴细胞/免疫学 动物 女(雌)性 人类 男(雄)性 小鼠 

摘      要：In order to understand better the mechanism of inhibitor formation in hemophilia A patients, we have characterized the immune response to human factor VIII in a murine model of hemophilia A. Mice with severe factor VIII deficiency caused by targeted gene disruptions in exons 16 and 17 were injected intravenously with human factor VIII. Anti-factor VIII was absent or was detected at only very low levels in hemophilic mice of both strains after a single injection of 0.2 mu g factor VIII, but it was present in most mice after a second exposure. Subsequent exposures led to high titer anti-factor VIII antibodies in both ELISA and inhibitor assays. A human factor VIII-specific T cell proliferative response was detected with spleen cells obtained three days after a single injection with human factor VIII, before mice had delectable anti-factor VIII antibodies. Subsequent exposures to factor VIII were followed by an increased T cell proliferative response. These studies indicate that murine hemophilia A is a good model for the study of the immune response to human factor VIII, especially the role of the T cell in the early steps in inhibitor antibody formation.