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 apoptosis-inducing signals into activated and/or autoreactive peripheral T and B cells by stimulation with Fas ligand or agonistic anti-Fas mAb. The i.p. administration of the hamster anti-mouse Fas mAb RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given another hamster anti-mouse Fas mAb Jo2 rapidly die of fulminant hepatitis with hemorrhage. Here, we report that MRL-gld/gld mice thoroughly recovered and/or were prevented from glomerulonephritis, arthritis, sialadenitis, vasculitis and lymphoadenopathy after receiving a single administration of the agonistic anti-mouse Fas mAb RK-8. The serum levels of autoantibodies were decreased after the administration. All the therapeutic effects of RK-8 persisted for >6 months. These findings suggest that the systemic administration of agonistic anti-Fas mAb without fulminant hepatitis-inducing activity is a useful therapeutic strategy for treating systemic autoimmune disease.