Studies on Collagen II Induced Arthritis in Mice and Rats

(1) The disease course after immunization of male DBA/ 1 mice with native mouse collagen I1 is characterized by a slow and progressive onset of disease and by frequent exacerbations of disease in both previously affected and previously nonaffected joints. On the other hand, after immunization with heterologous native collagen 11, there is seen a rapid and aggressive onset of disease with few exacerbations (as has been described by other authors).’ More than 50% of all immunized male mice acquired arthritis within 20 weeks, whereas none of the similarly immunized female littermates demonstrated arthritis within this time. (2) Antibody titers against mouse collagen I1 do not correlate with arthritis development, neither after immunization with mouse collagen nor after immunization with collagen of rat, cow, chick, and human origin. Instead, the amounts of autoantibodies towards collagen I1 were dependent on the immunogen used for immunization. Thus, in general, immunization with heterologous collagens gave higher autoantibody titers than immunization with mouse collagen, irrespective of the development of arthritis. ( 3 ) Immunohistochemical studies on the synovial tissue, particularly the pannus region, of arthritis rats immunized with native bovine collagen I1 showed that T “helper” cells dominate the lymphoid infiltrates, that many class I1 transplantation antigen-expressing cells are present in the synovial lining and in the pannus close to the damaged cartilage, and that few, if any, B cells/plasma cells are present within the synovial tissue early in the course of arthritis.’~~ (4) Lines and clones of collagen I1 specific T helper cells grown in vitro induce an aggressive synovitis in both untreated and irradiated (750 rad) syngeneic recipient DBA/ 1 mice! Injection of purified monoclonal antibodies reactive with native mouse collagen I1 in amounts of up to 5 mg per mouse did, however, only give rise to a relatively mild synovitis.