AMELIORATION OF SYSTEMIC AUTOIMMUNE-DISEASE BY THE STIMULATION OF APOPTOSIS-PROMOTING RECEPTOR FAS WITH ANTI-FAS MAB

Fas antigen (Fas) is a cell surface receptor molecule that mediates ap optosis-inducing signals into activated and/or autoreactive peripheral T and B cells by stimulation with Fas ligand or agonistic anti-fas mA b. The i.p. administration of the hamster anti-mouse Fas mAb RK-8, whi ch induced apoptosis both in vivo and in vitro, did not kill adult mic e, whereas those given another hamster anti-mouse Fas mAb Jo2 rapidly die of fulminant hepatitis with hemorrhage. Here, we report that MRL-g ld/gld mice thoroughly recovered and/or were prevented from glomerulon ephritis, arthritis, sialadenitis, vasculitis and lymphoadenopathy aft er receiving a single administration of the agonistic anti-mouse Fas m Ab RK-8. The serum levels of autoantibodies were decreased after the a dministration. All the therapeutic effects of RK-8 persisted for > 6 m onths. These findings suggest that the systemic administration of agon istic anti-fas mAb without fulminant hepatitis-inducing activity is a useful therapeutic strategy for treating systemic autoimmune disease.