Suppression of type II collagen–induced arthritis by monoclonal antibodies

Abstract

Some mouse monoclonal antibodies raised against chicken type I1 collagen suppressed or delayed the onset of chicken type I1 collagen-induced arthritis in DBA/l mice. This was correlated with the suppression of anti-mouse type I1 collagen antibody responses following immunization with chicken type I1 collagen. The epitopes recognized by the suppressive antibodies were found to be present on cyanogen bromide (CB)Aigested collagen peptides CB-11 and CB-12. This was also confirmed by the finding that administration of the CB-11 or CB-12 peptide suppressed the induction of arthritis.Immunization with native chicken type I1 collagen (CII) is known to cause arthritis in animals (1-3). Collagen-induced arthritis can also be adoptively transferred by sensitized spleen cells, and can be induced by passive transfer with anti-type I1 collagen antibodies (4). Moreover, for the development of arthritis, a specific epitope of collagen is important:From the Tsukuba Research Laboratories, Esai Co., Ibaraki, Japan; the Veterans Administration Hospital Medical Center, Memphis, Tennessee; and the School of Medicine, Chiba University, Chiba, Japan.Seiichi Immunization with the cyanogen bromide (CB)-digested type I1 collagen peptide 11 (CB-11 peptide), but not with other peptides, successfully induced arthritis in DBA/l mice (5). This indicates that the CB-11 peptide, rather than other portions of collagen, has an immunogenic epitope important in the induction of arthritis in the mouse.Conversely, recent studies have demonstrated that the immune response to collagen, as well as the induction of arthritis, can be modified by free collagen or anticollagen antisera (6). Administration of collagen-coupled spleen cells, native CII, a specific CB peptide, or polyclonal anti-CII before immunization with type I1 collagen results in the suppression or delayed onset of collagen-induced arthritis (6-9). Since the suppression of arthritis can be transferred by administration of splenic T cells obtained from the suppressed donor, type I1 collagen is thought to possess epitopes important for the suppression, as well as the induction, of anti-CII responses or arthritis (10).In this study, we successfully isolated monoclonal antibodies (MAb) against collagen peptides that inhibit type I1 collagen-induced arthritis. We also demonstrated that the epitopes important for the suppression of arthritis are located on the CB-11 and CB-12 peptides. MATERIALS AND METHODSMice. Male D B N l J mice (H-2q), ages 6-10 weeks, were obtained from Jackson Laboratories (Bar Harbor, ME) BALBIc mice, ages 10-20 weeks, were obtained from Charles River Japan (Atsugi, Kanagawa, Japan). All animals were housed in a barrier system and fed standard rodent chow and water ad libitum.

T cell regulation of collagen‐induced arthritis in mice. II. Immunomodulation of arthritis by cytotoxic T cell hybridomas specific for type II collagen

“…On the other hand, the injection of a CD4+ cell line reacting with CII was reported to protect against subsequent CIA induction provided that high numbers of cells were used [8]. Moreover, successful suppression of murine CIA was achieved with monoclonal antibodies reacting with determinants present on cyanogen bromide (CB) fragments of CII peptides, CBll and CB12 [ll].These data are in line with the identification of an immunosuppressive epitope within CBll (11) that confers protection against CIA [12]. Alternatively, the role of CD8+ cells in CIA is poorly documented.…”