EphrinB1-EphB signaling regulates thymocyte-epithelium interactions involved in functional T cell development.
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.
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain.
David
D
Alfaro
José J
JJ
García-Ceca
Teresa
T
Cejalvo
Eva
E
Jiménez
Eric J
EJ
Jenkinson
Graham
G
Anderson
Juan J
JJ
Muñoz
Agustín
A
Zapata
D000818:Animals; D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival; D036387:Ephrin-B1 / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D005333:Fetus; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D036081:Receptors, Eph Family / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D017252:CD3 Complex; D036387:Ephrin-B1; D036081:Receptors, Eph Family