title: Definitive engagement of cytotoxic CD8 T cells in C protein-induced myositis, a murine model of polymyositis.
abstract: OBJECTIVE
  To substantiate a pathogenic role of cytotoxic CD8 T cells in the development of a murine polymyositis model, C protein-induced myositis (CIM).
  
  
  METHODS
  Beta(2)-microglobulin-null mutant, perforin-null mutant, and wild-type (WT) C57BL/6 mice were immunized with skeletal muscle C protein fragments to provoke CIM. Regional lymph node CD8 or CD4 T cells stimulated with C protein-pulsed dendritic cells were transferred adoptively to naive mice. Inflammation and damage of the muscle tissues were evaluated histologically.
  
  
  RESULTS
  The incidence of myositis development was significantly lower in β₂-microglobulin-null and perforin-null mutant mice compared with WT mice. Inflammation was less severe in mutant mice, and the incidence of muscle injury was reduced significantly. Adoptive transfer of lymph node T cells from mice with CIM induced myositis in naive recipient mice. The CD8 T cell-induced muscle injuries were significantly more severe than the CD4 T cell-induced muscle injuries.
  
  
  CONCLUSIONS
  Perforin-mediated cytotoxicity by CD8 T cells is definitively responsible for muscle injury in CIM.
authors.affiliation: Tokyo Medical and Dental University, Tokyo, and Yokohama Institute, RIKEN, Yokohama, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sugihara
authors.forename: Naoko
authors.initials: N
authors.lastname: Okiyama
authors.forename: Mihoko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kuniko
authors.initials: K
authors.lastname: Kohyama
authors.forename: Yoh
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohsaka
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017285:Polymyositis / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000276:immunology*
chemical_list: D052899:Pore Forming Cytotoxic Proteins; D001613:beta 2-Microglobulin; C483886:perforin, mouse