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

Abstract

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.

• Authors: Yves Allenbach, Sounkary Solly, Sylvie Grégoire, Odile Dubourg, Benoit Salomon, Gillian Butler-Browne, Lucile Musset, Serge Herson, David Klatzmann, Olivier Benveniste
• Journal: The American journal of pathology (Am J Pathol) Vol. 174 Issue 3 Pg. 989-98 (Mar 2009) ISSN: 1525-2191 [Electronic] United States
• PMID: 19218348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-2 Receptor alpha Subunit
• Myosins

Topics

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