HUMAN MONOCLONAL RHEUMATOID FACTORS AUGMENT ARTHRITIS IN MICE BY THE ACTIVATION OF T-CELLS

In order to investigate the in vivo role of rheumatoid factor (RF), th e effects of the administration of human monoclonal (m) IgM-RF and IgG -RF on the development of arthritis in mice were examined. The adminis tration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups recei ving RF (RF-enhanced arthritis). Skin ulcers were also observed in som e of these RF-enhanced arthritis mice, whereas no such signs were obse rved in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increa sed CII-specific IgG antibodies in circulation and the severity of art hritis correlated with the production of high titres of anti-CII antib odies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD 4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immun odeficient (SCID) mice with arthritis developed by the transfer of spl een cells from CII-immunized mice, prolonged the arthritis and enhance d the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.