EphrinB1-EphB signaling regulates thymocyte-epithelium interactions involved in functional T cell development

Authors

  • David Alfaro,

    1. Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
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    • The first two authors contributed equally to this work.

  • José J. García-Ceca,

    1. Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
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    • The first two authors contributed equally to this work.

  • Teresa Cejalvo,

    1. Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
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  • Eva Jiménez,

    1. Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain
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  • Eric J. Jenkinson,

    1. MRC Center for Immune Regulation, Division of Immunity and Infection, Institute For Biomedical Research, Medical School, University of Birmingham, Edgbaston, Birmingham, UK
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  • Graham Anderson,

    1. MRC Center for Immune Regulation, Division of Immunity and Infection, Institute For Biomedical Research, Medical School, University of Birmingham, Edgbaston, Birmingham, UK
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  • Juan J. Muñoz,

    1. Microscopy and Cytometry Center, Complutense University, Madrid, Spain
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  • Agustín Zapata Dr.

    Corresponding author
    1. Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
    • Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain, Fax: +34-91-3944191
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Abstract

The Eph and ephrin families are involved in numerous developmental processes. Recently, an increasing body of evidence has related these families with some aspects of T cell development. In the present study, we show that the addition of either EphB2-Fc or ephrinB1-Fc fusion proteins to fetal thymus organ cultures established from 17-day-old fetal mice decreases the numbers of both double-positive (CD4+CD8+) and single-positive (both CD4+CD8 and CD4CD8+) thymocytes, in correlation with increased apoptosis. By using reaggregate thymus organ cultures formed by fetal thymic epithelial cells (TEC) and CD4+CD8+ thymocytes, we have also demonstrated that ephrinB1-Fc proteins are able to disorganize the three-dimensional epithelial network that in vivo supports the T cell maturation, and to alter the thymocyte interactions. In addition, in an in vitro model, Eph/ephrinB-Fc treatment also decreases the formation of cell conjugates by CD4+CD8+ thymocytes and TEC as well as the TCR-dependent signaling between both cell types. Finally, immobilized EphB2-Fc and ephrinB1-Fc modulate the anti-CD3 antibody-induced apoptosis of CD4+CD8+ thymocytes in a process dependent on concentration. These results therefore support a role for Eph/ephrinB in the processes of development and selection of thymocytes as well as in the establishment of the three-dimensional organization of TEC.

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