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

D Alfaro, JJ Garcia-Ceca, T Cejalvo, E Jiminez, Eric Jenkinson, Graham Anderson, JJ Munoz, A Zapata

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41 Citations (Scopus)


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 CD4(-)CD8(+)) 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.
Original languageEnglish
Pages (from-to)2596-605
Number of pages10
JournalEuropean Journal of Immunology
Issue number9
Publication statusPublished - 1 Sept 2007


  • Eph
  • thymic epithelial cell
  • ephrin
  • thymus
  • T cell differentiation


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