Activation of T-cells during the immune response is accompanied by increases in cell growth and signalling through the nutrient-sensitive mTOR pathway (to downstream components of the mRNA translational machinery) only in the presence of external amino acids (Fumarola et al. 2005). T-cell activation is also associated with increased surface expression of CD98, the glycoprotein subunit of the System L amino acid transporter (Verrey, 2003). We are currently investigating whether this transporter upregulation lies upstream or downstream of mTOR pathway activation and also whether transporter expression correlates with the regulation of T-cell size by the cytokine interleukin 2 (IL-2). Murine spleen-derived T-cells were activated via the T-cell receptor for 48h in suspension culture. Cells were subsequently incubated in the presence of either IL-2 (20 ng/ml) or medium alone for periods of up to 48h, with addition of a phosphotidylinositol 3-kinase (PI 3-K) inhibitor (LY294002; 10 μM) for the final 24h of certain experiments. System L transport function was assessed by cellular uptake of [³H]-phenylalanine using [¹⁴C]-inulin as an extracellular marker. CD98 surface expression was estimated by fluorescence activated cell sorting. Activated T-cells incubated with IL-2 exhibit phenylalanine transport (K_m = 15 μM, V_max = 85 ± 9 pmol/10⁶ cells/min; n = 3 cell preparations) with features characteristic of System L, notably a potent competitive inhibition by 2-amino-bicyclo [2,2,1] heptane-2-carboxylic acid (BCH; K_i = 9 μM) and a lack of Na⁺ dependence. Phenylalanine transport was not affected by change in external pH between 6.2 and 8.6. CD98 surface expression and System L transport function were both substantially reduced (by > 80%) in activated T-cells deprived of IL-2 for 24h. CD98 surface expression was also downregulated by LY294002 treatment of T-cells maintained in IL-2: this process also correlated with reduced transport activity. Western blotting of T-cell membrane proteins revealed that changes in CD98 expression were reflected by similar, IL-2 regulated, changes in expression of the catalytic System L subunit protein LAT1. The results show that activated T-cells express a functional System L transporter maintained at the cell surface by an IL-2 regulated, PI 3-kinase-dependent pathway. Regulated expression of this transporter may be important for control of T-cell growth and differentiation by the mTOR intracellular signalling pathway.