Pathogenesis of inflammatory arthropathy developed in HTLV-I transgenic mice

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We have recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T-cell leukemia virus type-1 (HTLV-1) genome (Iwakura et al., Science, 1991). The pathology was very similar to that of rheumatoid arthritis with synovial cell overgrowth, inflammatory cell infiltration, bone and cartilage erosion, and pannus formation (Rheum. Arth. 36,1612,1993), and moreover, a large proportion of the complex-type carbohydrate chains of the immunoglobulins lacked the terminal galactose residue (BBRC,192,1004,1993). In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines including IL-1alpha, IL-1beta, IL-2, IL-6, TNF-alpha, and IFN-gamma as well as MHC genes were activated in the transgenic joints (submitted). Interestingly, these mice produced antibodies against IgG,type II collagen (IIC), and heat shock proteins (HSPs) accompanied by IgG hypergammaglobulinemia. Thus, it was shown that HTLV-I can cause autoimmunity. Since development of arthritis was greatly affected by the genetic background of the mice, involvement of autoimmunity in the pathogenesis was suggested. These observations show that these mice are useful not only to analyze pathogenicity of rheumatoid arthritis but also to study pathogenicity of autoimmunity and roles of cytokines in its development. We are now studying retrovirus-host interactions in details using this transgenic mouse system.