Metabolic reprogramming and metabolic dependency in T cells


Correspondence to:

Douglas R. Green

Department of Immunology

MS 351, Room E7050

St. Jude Children's Research Hospital

262 Danny Thomas Place

Memphis, TN 38105-3678, USA

Tel.: +1 901 595 3488

Fax: +1 901 595 5766



Upon activation, quiescent naive T cells undergo a growth phase followed by massive clonal expansion and differentiation that are essential for appropriate immune defense and regulation. Accumulation of cell biomass during the initial growth and rapid proliferation during the expansion phase is associated with dramatically increased bioenergetic and biosynthetic demands. This not only requires a metabolic rewiring during the transition between resting and activation but also ‘addicts’ active T cells to certain metabolic pathways in ways that naive and memory T cells are not. We consider such addiction in terms of the biological effects of deprivation of metabolic substrates or inhibition of specific pathways in T cells. In this review, we illustrate the relevant metabolic pathways revealed by recent metabolic flux analysis and discuss the consequences of metabolic intervention on specific metabolic pathways in T lymphocytes.