Published online before print February 13, 2009

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(American Journal of Pathology. 2009;174:989-998.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080422

Role of Regulatory T Cells in a New Mouse Model of Experimental Autoimmune Myositis

Yves Allenbach^*, Sounkary Solly^*, Sylvie Grégoire^*, Odile Dubourg, Benoit Salomon^*, Gillian Butler-Browne^¶||, Lucile Musset^**, Serge Herson^*, David Klatzmann^* and Olivier Benveniste^*

From the UMR 7087,^* and UMRS787-Groupe Myologie,^¶ Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris; UMR 7087, the Centre National de la Recherche Scientifique (CNRS), Paris; the Institut de Myologie, the Service de Neuropathologie, the Laboratoire d’Immunochimie,^** and the Service de Médecine Interne 1, Hôpital Pitié-Salpêtriére, Assistance Publique-Hôpitaux de Paris, Paris; and the Institut de Myologie,|| INSERM, UMRS787; Paris, France

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.