Rathmell JC, Vander Heiden MG, Harris MH, Frauwirth KA, Thompson CB. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Molecular cell. 2000 Sep;6(6). 683-92. PMID: 11030347 [PubMed]
Without receptor stimulation, cells from multicellular organisms die by apoptosis. Here we show that lymphocytes deprived of receptor stimulation undergo progressive atrophy before commitment to apoptosis. Following loss of receptor engagement, lymphocytes rapidly downregulated the glucose transporter, glut1. This was accompanied by reduction in mitochondrial potential and cellular ATP, suggesting that atrophy resulted from depletion of glucose-derived metabolic substrates. Expression of the antiapoptotic protein, Bcl-X(L), prevented death but not atrophy following either growth factor or glucose withdrawal. In Bcl-X(L) transgenic animals, size and metabolic activity of naive T cells were regulated through the TCR and correlated with TCR-dependent glut1 expression. These data suggest that ligands for cell-specific receptors promote cell survival by regulating nutrient uptake and utilization.