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)alphabeta 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.
Swainson
Louise
L
Institut de Génétique Moléculaire, Unité Mixte de Recherche 5535, Montpellier, Cedex 5, France.
Kinet
Sandrina
S
Manel
Nicolas
N
Battini
Jean-Luc
JL
Sitbon
Marc
M
Taylor
Naomi
N
D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002453:Cell Cycle; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005947:Glucose / Q000494:pharmacology; D051272:Glucose Transporter Type 1; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007223:Infant; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D015703:Antigens, CD; C068126:CD71 antigen; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019718:Receptors, CXCR4; D011990:Receptors, Transferrin; C495677:SLC2A1 protein, human; D005947:Glucose