Costimulatory role of CXCR4 with pre-TCR and its crosstalk with PI3K in beta-selection of thymocytes. 
Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development.  Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-coupled receptor-in thymocyte development, particularly during the beta-selection developmental checkpoint.  Phosphotidylinositol 3-kinase interacts with the pre-T cell receptor and CXCR4 during migration, proliferation, and differentiation of developing thymocytes.  CXCR4 and Notch signaling, along with inhibition of glycogen synthase kinase-3beta (GSK-3beta), are essential for the proliferation and differentiation of thymocytes during beta-selection.  Thus, a critical role of chemokines and its downstream signaling in the beta-selection of thymocytes has been demonstrated.