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

Research output: Contribution to journalArticle

Authors

  • D Alfaro
  • JJ Garcia-Ceca
  • T Cejalvo
  • E Jiminez
  • JJ Munoz
  • A Zapata

Colleges, School and Institutes

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 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.

Details

Original languageEnglish
Pages (from-to)2596-605
Number of pages10
JournalEuropean Journal of Immunology
Volume37
Issue number9
Publication statusPublished - 1 Sep 2007

Keywords

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