T cell metabolic reprogramming and plasticity

• T cells undergo a metabolic rewiring during activation and differentiation.
• T cells are capable of responding to and adapting to nutrient fluctuations.
• T cells change metabolic substrates and routes in response to nutrient fluctuations.
• Metabolic plasticity allows T cells to maintain metabolic homeostasis.

Upon antigen stimulation, small and quiescent naïve T cells undergo an approximately 24 h growth phase followed by rapid proliferation. Depending on the nature of the antigen and cytokine milieu, these proliferating T cells differentiate into distinctive functional subgroups that are essential for appropriate immune defense and regulation. T cells undergo a characteristic metabolic rewiring that fulfills the dramatically increased bioenergetic and biosynthetic demands during the transition between resting, activation and differentiation. Beyond this, T cells are distributed throughout the body and are able to function in a wide range of physio-pathological environments, including some with a dramatic metabolic derangement. As such, T cells must quickly respond to and adapt to fluctuations in environmental nutrient levels. We consider such responsiveness and adaptation in terms of metabolic plasticity, that is, an evolutionarilly selected process which allows T cells to illicit robust immune functions in response to either a continuous or disrupted nutrient supply. In this review, we illustrate the relevant metabolic pathways in T cells and discuss the ability of T cells to change their metabolic substrates in response to changes in the environment.