International Immunology, Vol 9, 1793-1799, Copyright © 1997 by Oxford University Press
Y Nishimura-Morita, M Nose, T Inoue and S Yonehara
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.
ARTICLES
Amelioration of systemic autoimmune disease by the stimulation of apoptosis-promoting receptor Fas with anti-Fas mAb
The Pharmaceutical Basic Research Laboratories, JT Inc., Yokohama, Japan.
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