Original Paper

Cell Death and Differentiation (2005) 12, 463–472. doi:10.1038/sj.cdd.4401611 Published online 18 March 2005

Thymic myoid cells protect thymocytes from apoptosis and modulate their differentiation: implication of the ERK and Akt signaling pathways

Edited by RA Knight

R Le Panse1 and S Berrih-Aknin1

1CNRS UMR 8078, IPSC, Université Paris XI, Hôpital Marie Lannelongue, Le Plessis-Robinson, France

Correspondence: R Le Panse, CNRS UMR 8078, IPSC, Université Paris XI, Hôpital Marie Lannelongue, Le Plessis-Robinson, France. Tel: +33 01 40 94 28 00 ext 35 65; Fax: +33 01 46 30 45 64; E-mail: rozen.lepanse@ccml.u-psud.fr

Received 6 December 2004; Accepted 10 January 2005; Published online 18 March 2005.

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Abstract

Thymic myoid cells correspond to a muscle-like cell population present in the thymic medulla. They are well conserved throughout species evolution, but their biological role is not known. We demonstrated that myoid cells protected thymocytes from apoptosis as evidenced by a strong decrease of annexin-V-FITC positive thymocytes. 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 2 h in cocultures. This protective phenomenon was due to the activation of prosurvival mechanisms. Indeed, myoid cells activated extracellular-regulated kinases (ERK1/2) and Akt in thymocytes. Myoid cells also influenced thymocyte maturation. We observed an increase in CD4+ and a decrease in CD8+ single positive (SP) thymocytes when cocultured with myoid cells, independently of a CD8+SP increased death or a CD4+SP overproliferation. Consequently, thymic myoid cells protect thymocytes from apoptosis and could also modulate their differentiation process.

Keywords:

muscle-like cells, thymocytes, survival, differentiation, thymus

Abbreviations:

MITC, myoid immortalized thymic cells; TEC, thymic epithelial cells; MAPK, mitogen-activated protein kinase; ERK, extracellular-regulated kinase; PI3K, phosphatidylinositol 3-kinase; MHC, self-major histocompatibility complex; DN, double negative; DP, double positive; SP, single positive; TCR, T-cell receptor

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