Résumé :
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Introduction:Polymyositis (PM) and Inclusion body myositis (IBM) are inflammatory myopathies caraterized by invaded muscle fibers by autoreactive CD8+ T cells. Immunosupressive drugs used in PM are not always efficacious and have no effect on IBM evolution. We have previously shown the positive effect of regulatory T cells (Treg) transfer in a mouse model of experimental autoimmune myositis (EAM) that we developed. In attempt to develop new therapeutic approach we have tested in our mouse model the effect of rapamycin and/or IL-2, molecules known for their positive effect on Treg.Method :For EAM, mice were immunized once a week for 3 weeks with myosin emulsified in complete Freund's adjuvant. Muscle strength was tested by a clinical score measuring the time the mouse was able to stay hanged. The histological severity of muscular inflammation was graded using the Kojima Score (raging from 0: no inflammation to grade 4: diffuse, extensive infiltration). Mice received rapamacyne (3 mg/Kg/j) and/or IL-2 (25 000 U, 3 times a week) during immunization protocol. Results were compared to a control group receiving placebo. Results:In rapamycine treated mice, myositis was significantly less severe attested by the clinical (285±152 s. vs 72±14 s., p = 0.05) and the histological scores (0,8±0,75 vs 3,25±0,7, p = 0.001). Administratition of IL-2 alone had no effect on disease progression. With a combined treatment (IL-2 and Rapamycine), there is no supplementary benefice compare to rapamacyne alone.Treatment with rapamycine alone is associated with a significant decrease of lymphocyte count in draining lymph nodes (26,6±9.6X106 vs 51.3±11.3X106 p = 0.006). The decrease concerns only T cells compartment (32±12% vs 72±4,5%) and spare B cells (61±6% vs 33±14%).Conversely, rapamycine treatment permits a significant increase of the Treg percentage in draining lymph nodes (14,9±1,2% vs 9,4±1,8% p = 0.004). Rapamycine do not modify the ability of effector T cells to produce l'INF or l'IL-17.ConclusionTogether these results show the efficacy of rapamycine to reduce the severity of the myositis in a model of experimental auto-immune myositis. The increased percentage of Treg associated with the decreased percentage of T cells suggest an improvement Treg / autoreactive effector T cell ratio.These encouraging results permit to consider to treat auto-immune myositis with rapamycin.
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