Résumé :
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Myasthenia Gravis (MG) is an autoimmune disease characterized by antibody-mediated dysfunction of the neuromuscular junction. Regulatory CD4+CD25+Foxp3+ T cells (Treg) are responsible for maintenance of the peripheral self-tolerance. Our previous study showed a severe functional defect of thymic Treg of MG patients, while their number, as evaluated by the CD25 marker, was normal. The aim of the study was to investigate the causes of Treg functional defect. 1) We first investigated whether this defect was thymic-specific or could also be found in the periphery. Functional studies using peripheral Tregs confirmed that they display a functional defect in suppressive activity, similar to Tregs isolated from the thymus. These results emphasize that the defect is not only related to the activation status of MG thymuses, but is probably intrinsic. 2) Since the CD4+CD25+ population includes both Treg (FoxP3-positive, IL-7alpha receptor-negative) and effector cells (FoxP3-negative, IL-7alpha receptor-positive), we wondered whether the functional defect in MG Tregs could be explained by the presence of effector cells in the CD4+CD25+ population studied. Analysis of FoxP3 and of IL-7a receptor showed that the numbers of effector T cells were not increased in MG patients, either in the thymus or at the periphery. 3) FoxP3 is normally inducible by activation of CD4+CD25- cells. We observed that inducibility of FoxP3 in CD4+CD25- T cells is less efficient in MG patients than in control individuals, suggesting that the ability of CD4+CD25- to become CD4+CD25+Foxp3+ Treg with suppressive activity may be affected. The low inducibility of FoxP3 in MG cells suggests a defect of FoxP3 regulation that could be related to the functional defect.
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