Treatment of lupus in NZB/W F1 mice with monoclonal antibody against Fas ligand.
Since Fas ligand (FasL) can induce apoptosis of Fas-bearing cells, Fas/FasL interactions can play a critical role in maintaining self-tolerance. Fas/FasL interactions in lupus-like autoimmune disease have been well characterized in studies using either Fas or FasL mutant mice. However, the effect of the defective FasL-mediated signaling on the establishment of lupus in other mouse strains, such as NZB/W (B/W) F1, remains uncertain. In the present study, we examined the effect of anti-FasL monoclonal antibody (mAb) on the development of lupus. Treatment of B/W F1 mice with anti-FasL mAb augmented IgG1- and IgG2a-type anti-dsDNA Ab production. However, treatment of B/W F1 mice with anti-FasL mAb also significantly prevented the development of lupus nephritis. These results indicate that Fas/FasL interactions not only regulate IgG-type autoantibody production, but also influence the development of lupus nephritis in B/W F1 mice.
Nakajima
A
A
Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, 113-8603, Japan. amnakaji@aol.com
Hirai
H
H
Kayagaki
N
N
Yoshino
S
S
Hirose
S
S
Yagita
H
H
Okumura
K
K
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D053222:Fas Ligand Protein; D005260:Female; D006824:Hybridization, Genetic; D007074:Immunoglobulin G / Q000097:blood; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins