Development of humanized mice as a model of inflammatory arthritis

Clinically, rheumatoid arthritis (RA) is a chronic deforming disease characterized mainly by joint swelling and destruction. Although synovial inflammation and bone erosion are the hallmarks of this disease, the presentation of various features between patients is clearly heterogenous, suggesting that there are different variants of RA. Hence, the development of an animal model that has all of the elements of human RA has remained elusive. This review explores several different views on the etiology of RA and the recent data from various murine arthritis models which provide support for these theories. In addition to discussing the potential roles of CD4(+) T cell activation, autoantibodies, and lymphocyte-independent cytokine production, the role of CD4(+) T regulatory cells will be presented in the context of a newly developed humanized transgenic mouse model. This novel T cell receptor transgenic model is being characterized to enhance our understanding of the mechanisms involved in the breach of self-tolerance that occurs in autoimmune disorders such as RA.