Potent adjuvant effect by anti-CD40 in collagen-induced arthritis. Enhanced disease is accompanied by increased production of collagen type-II reactive IgG2a and IFN-gamma

Collagen type II-induced arthritis (CIA) is an experimental model of rheuma toid arthritis, an autoimmune inflammatory disease of the peripheral joints in humans. CD40 interaction with its ligand CD154 (CD40L) has been shown t o be an obligatory step in the initiation of autoimmune disease in several animal models. In this study we report on the effect of CD40 stimulation in CIA induced by immunization with type II collagen (CII) in CFA or IFA. We found that the administration of stimulatory anti-CD40 mAb resulted in earl ier onset and more severe disease in IFA-CII-immunized mice. The mAb treatm ent resulted in markedly elevated titers of CII-specific IgG2a antibodies w hereas CII-specific IgG1 titers were unaffected. Draining lymphnode cell cu ltures from mice treated with anti-CD40 exhibited significantly increased I FN-gamma production compared to cultures from control antibody-treated mice . In conclusion, our results indicate that the level of CD40 activation dur ing the induction of an autoimmune response may determine the severity of t he resulting disease. (C) 2000 Academic Press.