Definitive engagement of cytotoxic CD8 T cells in C protein-induced myositis, a murine model of polymyositis

Arthritis Rheum. 2010 Oct;62(10):3088-92. doi: 10.1002/art.27625.


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.

Conclusion: Perforin-mediated cytotoxicity by CD8 T cells is definitively responsible for muscle injury in CIM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polymyositis / immunology*
  • Pore Forming Cytotoxic Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • beta 2-Microglobulin / immunology*


  • Pore Forming Cytotoxic Proteins
  • beta 2-Microglobulin
  • perforin, mouse