Mice lacking mature T and B lymphocytes develop arthritic lesions after immunization with type II collagen.

Collagen-induced arthritis in DBA/1 mice is a widely used experimental model of rheumatoid arthritis. The induction phase of the disease is thought to be dependent upon MHC-restricted T and B cell-mediated immune responses to type II collagen, but an influence of additional non-MHC-restricted mechanisms has also been proposed. In this study, we report that type II collagen immunization of DBA/1 mice lacking mature T and B lymphocytes resulted in the development of arthritic lesions, which were characterized by synovial hyperplasia with occasional inflammation as well as cartilage and bone destruction. The specificity of disease induction to type II collagen was confirmed, because arthritis could not be induced when control preparations of OVA or adjuvant alone were administered. A delay in clinical disease onset and a reduction in severity between lymphocyte-positive and -negative DBA/1 mice confirmed that lymphocytes play an important role in disease; however, similar pathologic features and normal incidence suggest that lymphocyte-independent mechanisms of disease induction also operate in the standard collagen-induced arthritis model. We conclude that adaptive immune responses are not the only arthritogenic mechanism and hypothesize that the nonantigenic properties of type II collagen can also lead to arthritis.