title: Downregulation of RCAS1 and upregulation of cytotoxic T cells affects synovial proliferation and apoptosis in rheumatoid arthritis.
abstract: OBJECTIVE
  The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells. This seems to be the result of the proliferation and apoptosis induced by immune balance. We studied the involvement of RCAS1 and the infiltration of cytotoxic T lymphocytes (CTL), and examined the synovium immunohistochemically to determine the involvement of proliferation and apoptosis in synovial lining cells, and their relationship with the activity of RATreg cells in the germinal center.
  
  
  METHODS
  We used double-immunological staining of Ki-67 and caspase-3 to investigate proliferation and apoptosis. We analyzed CTL, regulatory T cells (Treg), and receptor-binding cancer antigen expressed on SiSo cells (RCAS1), recently recognized to play a role in immune evasion. Proliferation and apoptosis were more frequently encountered in synovial lining cells in RA than in those in osteoarthritis (OA) that were used as a control.
  
  
  RESULTS
  High expression of RCAS1 was detected more frequently in the synovial lining cells of OA, but CTL infiltration into the synovium was rarely found. In RA, on the other hand, CTL were observed, while RCAS1 expression was lacking. We compared the presence of Foxp3-positive cells with the level of C-reactive protein (CRP) that served as an active inflammatory marker. Foxp3-positive cells in the germinal center and in CRP showed possible correlation in terms of the range of inflammatory states.
  
  
  CONCLUSIONS
  In RA, the lack of RCAS1 is thought to induce CTL infiltration through loss of the ability to evade immune attack, thus leading to apoptosis of the synovial lining cells. In addition, Treg cells may play a role in the downregulation of activated T cells.
authors.affiliation: Department of Pathology, School of Medicine, Kurume University, Kurume, Japan. marine7blue@hotmail.com
authors.forename: Shiro
authors.initials: S
authors.lastname: Yoshida
authors.forename: Fujio
authors.initials: F
authors.lastname: Higuchi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Goto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nomura
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Karube
authors.forename: Kei
authors.initials: K
authors.lastname: Shimizu
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Aoki
authors.forename: Hideki
authors.initials: H
authors.lastname: Komatani
authors.forename: Keiko
authors.initials: K
authors.lastname: Hashikawa
authors.forename: Yoshizo
authors.initials: Y
authors.lastname: Kimura
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
authors.forename: Kensei
authors.initials: K
authors.lastname: Nagata
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; C120762:EBAG9 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D002097:C-Reactive Protein; D053148:Caspase 3