Role of regulatory T cells in a new mouse model of experimental autoimmune myositis

Am J Pathol. 2009 Mar;174(3):989-98. doi: 10.2353/ajpath.2009.080422. Epub 2009 Feb 13.


Polymyositis is a rare and severe inflammatory muscle disorder. Treatments are partially efficacious but have many side effects. New therapeutic approaches must be first tested in a relevant animal model. Regulatory CD4+CD25+ T cells (Tregs) have been rediscovered as a pivotal cell population in the control of autoimmunity, but the connection between polymyositis and Tregs is currently unknown. To develop a reproducible experimental autoimmune myositis model of polymyositis, mice were immunized once a week for 3 weeks with 1 mg of partially purified myosin emulsified in complete Freund's adjuvant. All mice injected with myosin and complete Freund's adjuvant developed myositis. The infiltrates were composed of CD4(+) and CD8(+) cells, as well as macrophages, but did not contain B lymphocytes. In mice that were depleted of Tregs, the myositis was more severe, as determined by quantitative scoring of muscle inflammation (2.36 +/- 0.9 vs. 1.64 +/- 0.8, P = 0.019). In contrast, injection of in vitro expanded polyclonal Tregs at the time of immunization significantly improved the disease (quantitative score of inflammation 0.87 +/- 1.06 vs. 2.4 +/- 0.67, P = 0.047). Transfer of sensitized or CD4(+)-sorted cells from the lymph nodes of experimental autoimmune myositis mice induced myositis in naïve, irradiated, recipient mice. Thus, experimental autoimmune myositis is a reproducible, transferable disease in mice, both aggravated by Treg depletion and improved by polyclonal Treg injection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Immunization
  • Immunohistochemistry
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Mice
  • Mice, Inbred BALB C
  • Muscle Strength
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myosins / physiology
  • Nervous System Autoimmune Disease, Experimental / immunology*
  • Nervous System Autoimmune Disease, Experimental / pathology
  • T-Lymphocytes, Regulatory / immunology*


  • Interleukin-2 Receptor alpha Subunit
  • Myosins