Résumé :
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Communication n° 509 Myoid cells, a rare cell population in the thymus, are localized in the thymic medulla and the cortico-medullary junction. They share common characteristics with skeletal muscle cells but their role is not clearly defined. As lympho-stromal interactions are crucial to determine the fate of thymocytes within the thymus, we investigated the role of myoid cells on thymocyte behavior in vitro. Using a human myoid cell line established in our laboratory, we demonstrated that in vitro co-culture of myoid cells and thymocytes protected thymocytes from apoptosis as evidenced by a strong decrease of annexin-V-FITC positive cells. This effect was (1) specific of myoid cells compared to thymic epithelial cells, (2) dependent on direct cell-to-cell contacts and (3) triggered rapidly after two hours in co-cultures. We investigated the intracellular mechanisms involved in this protective effect of myoid cells. We observed that myoid cells induce a prolonged phosphorylation of Extracellular-Regulated Kinases, ERK1/2 and Akt: Akt acting upstream of ERK1/2. We first observed that Akt and ERK1/2 activation were dependent on direct cell-to-cell contacts, as for the protective effect of myoid cells. Moreover, the inhibition of the Akt and ERK signaling pathways, using LY294002 or U0126 respectively, decreased in a dose dependent manner the protective effect of myoid cells. Myoid cells also influenced thymocyte maturation. We observed an increase in CD4+ and a decrease in CD8+ single positive (SP) thymocytes when co-cultured with myoid cells, independently of a CD8+SP increased death or a CD4+SP over-proliferation. Our observations demonstrate that thymic myoid cells contribute to the maturation process of thymocytes and to their protection from apoptosis.
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