T-cell metabolism governing activation, proliferation and differentiation: a modular view

T lymphocytes are a critical component of the adaptive immune system mediating protection against infection and malignancy, but also implicated in many immune pathologies. Upon recognition of specific antigens T cells clonally expand, traffic to inflamed sites and acquire effector functions, such as the capacity to kill infected and malignantly transformed cells and secrete cytokines to coordinate the immune response. These processes have significant bioenergetic and biosynthetic demands, which are met by dynamic changes in T-cell metabolism, specifically increases in glucose uptake and metabolism; mitochondrial function; amino acid uptake, and cholesterol and lipid synthesis. These metabolic changes are coordinate by key cellular kinases and transcription factors. Dysregulated T-cell metabolism is associated with impaired immunity in chronic infection and cancer and conversely with excessive T-cell activity in autoimmune and inflammatory pathologies. Here we review the key aspects of T-cell metabolism relevant to their immune function, and discuss evidence for the potential to therapeutically modulate T-cell metabolism in disease.