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 Fast mutant mice. However, the effect of the defective Fast-mediated signaling on the establishment of lupus in other mouse strains, such as NZB/W (B/W) Fl, remains uncertain. In the present study, we examined the effect of anti-Fast monoclonal antibody (mAb) on the development of lupus. Treatment of B/W Fl mice with anti-Fast mAb augmented IgG1- and IgG2a-type anti-dsDNA Ab production. However, treatment of B/W F1 mice with anti-Fast 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. (C) 2000 Academic Press.