Abstract
Eph kinases are the largest family of receptor tyrosine kinases, and their ligands, ephrins (EFNs), are also cell surface molecules. In this study, we investigated the role of EFNB1 and the Ephs it interacts with (collectively called EFNB1 receptors) in mouse T-cell development. In the thymus, CD8 single positive (SP) and CD4CD8 double positive (DP) cells expressed high levels of EFNB1 and EFNB1 receptors, whereas CD4 SP cells had moderate expression of both. Soluble EFNB1-Fc in fetal thymus organ culture caused significant subpopulation ratio skew, with increased CD4 SP and CD8 SP and decreased DP percentage, while the cellularity of the thymus remained constant. Moreover, in EFNB1-treated fetal thymus organ culture, CD117(+), CD25(+), DP, CD4 SP, and CD8 SP cells all had significantly enhanced proliferation history, according to bromodeoxyuridine uptake. In vitro culture of isolated thymocytes revealed that EFNB1-Fc on solid-phase protected thymocytes from anti-CD3-induced apoptosis, with concomitant augmentation of several antiapoptotic factors, particularly in CD4 SP and CD8 SP cells; on the other hand, soluble EFNB1-Fc promoted anti-CD3-induced apoptosis, as was the case in vivo. This study reveals that EFNB1 and EFNB1 receptors are critical in thymocyte development.
Highlights
Receptors are important cell surface molecules for communication between cells and their environment
We showed that EFNB1 and EFNB1R were expressed differentially on thymocyte subpopulations; Fetal Thymus Organ Culture (FTOC) in the presence of soluble EFNB1-Fc had significant subpopulation ratio skew, possibly the result of disturbance due to apoptosis and proliferation of different subpopulations; solid-phase EFNB1 delivered survival signals via EFNB1R to the thymocytes, accompanied by modulation of certain antiapoptotic factors; and soluble EFNB1 promoted thymocyte apoptosis
These results suggest that EFNB1 and its receptors play important roles in thymocyte TCR signaling strength, which modulates thymocyte survival
Summary
Receptors are important cell surface molecules for communication between cells and their environment. The percentage of EFNB3Rpositive cells (lower row of Fig. 1B), as measured by EFNB3-Fc [18] binding, was low in most subpopulations (0% in DN, 3.2% in DP, and 0.3% in CD4 SP), with the exception of CD8 SP (11.4%), suggesting a more prominent role of EFNB1R than that of EFNB3 receptors in thymic T-cell development.
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