Role of regulatory T cells in a new mouse model of experimental autoimmune myositis.
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.
Allenbach
Yves
Y
UMR 7087, Université Pierre et Marie Curie, University of Paris 06, Paris, France.
Solly
Sounkary
S
Grégoire
Sylvie
S
Dubourg
Odile
O
Salomon
Benoit
B
Butler-Browne
Gillian
G
Musset
Lucile
L
Herson
Serge
S
Klatzmann
David
D
Benveniste
Olivier
O
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007114:Immunization; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D009218:Myosins / Q000502:physiology; D020721:Nervous System Autoimmune Disease, Experimental / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D053645:Interleukin-2 Receptor alpha Subunit; D009218:Myosins