title: Direct suppression of autoaggressive CD8+ T cells with CD80/86 blockade in CD8+ T cell-mediated polymyositis models of mice.
abstract: OBJECTIVE
  CD80/86 blockade to inhibit CD28 costimulation suppressed alloreactive human and murine CD4+ T cells but not alloreactive CD8+ T cells. In contrast, CD28 costimulation augments CD8+ T cell-mediated cell lysis in antigen-nonspecific stimulation. The present study was conducted to discern whether the CD80/86 blockade exerts therapeutic effects on CD8+ T cell-mediated polymyositis (PM) models of mice and whether the effects could be attributable to direct suppression of autoantigen-specific CD8+ T cells.
  
  
  METHODS
  C protein-induced myositis (CIM) was induced in mice with intradermal injection of C protein fragments. C protein peptide-induced myositis (CPIM), in which autoaggressive CD8+ T cells are activated without CD4+ T cell help, was induced in mice with intravenous injection of dendritic cells (DCs) loaded with CD8+ T cell-epitope peptides derived from the C protein fragment. The immunised mice were treated with CTLA4-Ig or anti-CD80 and anti-CD86 antibodies (anti-CD80/86 Abs). The muscles were evaluated histologically 21 days after the C protein immunisation or 7 days after the DC injection.
  
  
  RESULTS
  CIM was suppressed in the mice treated with CTLA4-Ig or anti-CD80/86 Abs administered prophylactically from the day of immunisation and therapeutically after the disease onset. CPIM was suppressed when CTLA4-Ig was administered concurrently with the DC injection.
  
  
  CONCLUSIONS
  The CD80/86 blockade was effective in PM models of mice. Amelioration of CPIM indicates direct suppression of CD8+ T cells by the CD80/86 blockade. CTLA4-Ig should be a potential therapeutic agent of PM and other CD8+T cell-mediated diseases by suppressing both autoantigen-specific CD4+ and CD8+ T cells.
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Kimito
authors.initials: K
authors.lastname: Kawahata
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Mizoguchi
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Okiyama
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. kohsaka.rheu@tmd.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohsaka
mesh_terms: D000069594:Abatacept / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000037:antagonists & inhibitors; D051940:B7-2 Antigen / Q000037:antagonists & inhibitors; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000276:immunology; D017285:Polymyositis / Q000276:immunology*
chemical_list: D000906:Antibodies; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D000069594:Abatacept