Type II collagen-induced arthritis (CIA) in mice and rats is an inflammatory polyarthritis that displays several characteristics similar to human rheumatoid arthritis (1, 2). The onset of CIA is associated with the development of both a cellular and humoral response to type II collagen (3) and is restricted in mice to animals of the H-2 q or H-2 r haplotype (4). The humoral response to type II collagen appears to be an essential element in the development of the disease although the role of cellular immunity is less clear.The L3T4 antigen, defined by a rat anti-mouse monoclonal antibody GK1.5, is limited to T cells responsible for class II major histocompatibility complex (MHC)-restricted functions and is analogous to the OKT4/Leu-3 antigen on human T cells (5, 6). Recent reports (7, 8) have indicated that treatment of murine experimental autoimmune diseases with monoclonal anti-L3T4 antibody under either preventive or therapeutic protocols dramatically decreases disease expression. In this paper we demonstrate the prevention of murine CIA by in vivo treatment with monoclonai antibody to the L3T4 antigen.
Materials and MethodsAnimals. DBA/1 male mice, 8-10 wk old, were obtained from The Jackson Laboratory, Bar Harbor, ME.Type H Collagen. Bovine articular cartilage was processed through four 24-h extractions with 5 vol of 4 M guanidine HCI, 50 mM Tris, pH 7.0, at 4°C. The slices were washed twice for 2 h in 1 M NaCI, 50 mM Tris, pH 7.5, once for 2 h in distilled H20, and twice for 3 h with 0.5 M HAc, and then digested overnight with 10 vol of 200 ttg/ml pepsin in 0.5 M HAc. The digest was centrifuged for 1 h at 10,000 g; solid NaCI was added to the supernatant to a concentration of 0.9 M and held overnight. After centrifugation, the pellet was resuspended in 5 vol of 1 M NaCI, 50 mM Tris, pH 7.5. The solution was adjusted to pH 8 by addition of 3 N NaOH and, after centrifugation as above, the supernatant was reprecipitated by the addition of solid NaC! to a final concentration of 4 M. After centrifugation, the pellet was suspended in 5 vol of 0.5 M HAc, dialyzed against 0.5 M HAc, and centrifugated at 27,000 g for 1 h. The purity of the type II collagen in the supernatant preparation was determined by sodium dodecyl sulphate gel electrophoresis, which showed a single band identical to a sample of pure bovine type II collagen (kindly provided by Dr.