title: Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis.
abstract: OBJECTIVE
  Although interleukin-17 (IL-17)-producing gamma/delta T cells were reported to play pathogenic roles in collagen-induced arthritis (CIA), their characteristics remain unknown. The aim of this study was to clarify whether gamma/delta T cells or CD4+ T cells are the predominant IL-17-producing cells, and to determine what stimulates gamma/delta T cells to secret IL-17 in mice with CIA. The involvement of IL-17-producing gamma/delta T cells in SKG mice with autoimmune arthritis and patients with rheumatoid arthritis (RA) was also investigated.
  
  
  METHODS
  IL-17-producing cells in the affected joints of mice with CIA were counted by intracellular cytokine staining during 6 distinct disease phases, and these cells were stimulated with various combinations of cytokines or specific antigens to determine the signaling requirements. Similar studies were performed using SKG mice with arthritis and patients with RA.
  
  
  RESULTS
  Gamma/delta T cells were the predominant population in IL-17-producing cells in the swollen joints of mice with CIA, and the absolute numbers of these cells increased in parallel with disease activity. IL-17-producing gamma/delta T cells expressed CC chemokine receptor 6, were maintained by IL-23 but not by type II collagen in vitro, and were induced antigen independently in vivo. Furthermore, IL-17 production by gamma/delta T cells was induced by IL-1beta plus IL-23 independently of T cell receptor. In contrast to what was observed in mice with CIA, IL-17-producing gamma/delta T cells were nearly absent in the affected joints of SKG mice and patients with RA, and Th1 cells were predominant in the joints of patients with RA.
  
  
  CONCLUSIONS
  Gamma/delta T cells were antigen independently stimulated by inflammation at affected joints and produced enhanced amounts of IL-17 to exacerbate arthritis in mice with CIA but not in SKG mice with arthritis or patients with RA.
authors: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Yoshinaga
authors: Y
authors: Ito
authors: Takashi
authors: T
authors: Usui
authors: Shio
authors: S
authors: Kobayashi
authors: Mikiko
authors: M
authors: Iguchi-Hashimoto
authors: Hiromu
authors: H
authors: Ito
authors: Hiroyuki
authors: H
authors: Yoshitomi
authors: Takashi
authors: T
authors: Nakamura
authors: Masakazu
authors: M
authors: Shimizu
authors: Daisuke
authors: D
authors: Kawabata
authors: Naoichiro
authors: N
authors: Yukawa
authors: Motomu
authors: M
authors: Hashimoto
authors: Noriko
authors: N
authors: Sakaguchi
authors: Shimon
authors: S
authors: Sakaguchi
authors: Hajime
authors: H
authors: Yoshifuji
authors: Takaki
authors: T
authors: Nojima
authors: Koichiro
authors: K
authors: Ohmura
authors: Takao
authors: T
authors: Fujii
authors: Tsuneyo
authors: T
authors: Mimori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D006614:Hindlimb; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007596:Joints / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate