title: Low CD4/CD8 T-cell ratio associated with inflammatory arthropathy in human T-cell leukemia virus type I Tax transgenic mice.
abstract: BACKGROUND
  Human T-cell leukemia virus type I (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL) as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A transgenic mouse that expresses HTLV-1 Tax also develops T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. The aim of this study was to identify the primary T-cell subsets involved in the development of arthropathy in Tax transgenic mice.
  
  
  RESULTS
  By 24 months of age, Tax transgenic mice developed severe arthropathy with a cumulative incidence of 22.8%. The pathological findings of arthropathy in Tax transgenic mice were similar to those seen in human rheumatoid arthritis or mouse models of rheumatoid arthritis, with synovial proliferation and a positive rheumatoid factor. Before the onset of spontaneous arthropathy, young and old Tax transgenic mice were not sensitive to collagen and did not develop arthritis after immunization with type II collagen. The arthropathic Tax transgenic mice showed a significantly decreased proportion of splenic CD4(+) T cells, whereas the proportion of splenic CD8(+) T cells was increased. Regulatory T cells (CD4(+)CD25(+)Foxp3(+)) were significantly decreased and CD8(+) T cells that expressed the chemokine receptor CCR4 (CD8(+)CCR4(+)) were significantly increased in arthropathic Tax transgenic mice. The expression of tax mRNA was strong in the spleen and joints of arthropathic mice, with a 40-fold increase compared with healthy transgenic mice.
  
  
  CONCLUSIONS
  Our findings reveal that Tax transgenic mice develop rheumatoid-like arthritis with proliferating synovial cells in the joints; however, the proportion of different splenic T-cell subsets in these mice was completely different from other commonly used animal models of rheumatoid arthritis. The crucial T-cell subsets in arthropathic Tax transgenic mice appear to resemble those in HAM/TSP patients rather than those in rheumatoid arthritis patients.
authors.affiliation: Division of Microbiology and Genetics, Center for Animal Resources and Development, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan. ohsugi@gpo.kumamoto-u.ac.jp
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohsugi
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018956:CD5 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002452:Cell Count; D024043:Collagen Type II / Q000009:adverse effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D054398:Receptors, CCR4 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism
chemical_list: D018956:CD5 Antigens; D024043:Collagen Type II; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016356:Gene Products, tax; D054398:Receptors, CCR4; C514970:tax protein, Human T-lymphotrophic virus 1