Glucose transporter 1 expression identifies a population of cycling CD4+CD8+ human thymocytes with high CXCR4-induced chemotaxis

GLUT1, the major glucose transporter in peripheral T lymphocytes, is induced upon T cell receptor activation. However, the role of GLUT1 during human thymocyte differentiation remains to be evaluated. Our identification of GLUT1 as the human T lymphotrophic virus (HTLV) receptor has enabled us to use tagged HTLV-receptor-binding domain fusion proteins to specifically monitor surface GLUT1 expression. Here, we identify a unique subset of CD4(+)CD8(+) double-positive (DP) thymocytes, based on their GLUT1 surface expression. Whereas these cells express variable levels of CD8, they express uniformly high levels of CD4. Glucose uptake was 7-fold higher in CD4(hi)DP thymocytes than in CD4(lo)DP thymocytes (P = 0.0002). Further analyses indicated that these GLUT1(+) thymocytes are early post-beta-selection, as demonstrated by low levels of T cell receptor (TCR)alpha beta and CD3. This population of immature GLUT1(+)DP cells is rapidly cycling and can be further distinguished by specific expression of the transferrin receptor. Importantly, the CXCR4 chemokine receptor is expressed at 15-fold higher levels on GLUT1(+)DP thymocytes, as compared with the DP GLUT1-subset, and the former cells show enhanced chemotaxis to the CXCR4 ligand CXCL12. Thus, during human thymopoiesis, GLUT1 is up-regulated after beta-selection, and these immature DP cells constitute a population with distinct metabolic and chemotactic properties.