A novel murine anti-human Fas mAb which mitigates lymphadenopathy without hepatotoxicity

Defects in Fas-mediated apoptosis are implicated in autoimmune diseases inc luding rheumatoid arthritis (RA), Although induction of Fas-mediated apopto sis could have therapeutic effects on these diseases, it might cause delete rious effects in liver as Fas ligand or an agonistic anti-murine Fas antibo dy Jo2 causes severe hepatic injury in mice. We report here on the interest ing characteristics of the newly obtained anti-fas mAb, HFE7A, which cross- reacts with the Fas molecules of various species ranging from human to mous e and mitigates autoimmune symptoms without hepatotoxicity in mice. The adm inistration of HFE7A to mice induced apoptosis in the thymocytes, although administration of HFE7A to mice or to marmosets did not induce any sign of hepatitis. The effect of HFE7A on liver is different from that of anti-muri ne Fas antibody Jo2, which causes acute and lethal hepatic injury to mice. Administration of HFE7A reduced lymphadenopathy and abnormal T cells in MRL -gld/gld mice. HFE7A induced apoptosis in synovial cells prepared from RA p atients. Surprisingly, HFE7A protected mice from fulminant hepatitis induce d by Jo2, Therefore, HFE7A is a potential therapeutic antibody not only for autoimmune diseases including RA but also for fulminant hepatitis.