CHANGES IN GLUCOSE-TRANSPORT AND TRANSPORTER ISOFORMS DURING THE ACTIVATION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES BY PHYTOHEMAGGLUTININ

We have explored the mechanism of stimulation of glucose transport dur ing PHA stimulation of human peripheral blood lymphocytes (HPBT) enric hed in T cells. Equilibrium exchange flux of 3-O-methyl glucose (3-O-M G) was stimulated two- and fourfold at 24 and 48 h after PHA stimulati on, respectively. The increase was transient in that the flux rate ret urned to control (unstimulated) levels by 96 h. Immunoblotting and imm unoprecipitation using specific Abs revealed that resting HPBT express es glucose transporter isoforms GLUT-2 and GLUT-3 but not GLUT-1. Afte r PHA stimulation, GLUT-1 expression was induced predominantly in the plasma membrane, whereas GLUT-3 expression was simultaneously down-reg ulated. GLUT-1 expression was detectable at 24 h, peaked at 48 h, and disappeared at 96 h. The total number of glucose transporters per cell measured as the total capacity of D-glucose displaceable cytochalasin B binding did not change significantly at any time after PHA stimulat ion. PHA stimulation also caused expression of high affinity IL-2R and secretion of IL-2. The IL-2 secretion was transient, which peaked at 24 h, Slightly preceding the GLUT-1 expression peak and disappeared at 72 h. In PHA-activated HPBT cells synchronized at G(0)-G(1), GLUT-1 w as not expressed but was rapidly induced by exposure to IL-2. This ind uction did not occur in the presence of cyclosporin A, which inhibits IL-2 secretion. Based on these observations, we conclude that PHA stim ulation increases glucose transport partly by inducing the expression of GLUT-1 instead of GLUT-3 and that GLUT-1 expression is induced by s ignals generated by IL-2 binding to its high affinity receptors.