Full effector function of TH1 cells requires that the cells switch to aerobic glycolysis. In Cell, Pearce and colleagues report post-transcriptional regulation of mRNA encoding IFN-γ and IL-2 mediated by the enzyme GAPDH when cells switch their metabolism from oxidative phosphorylation to aerobic glycolysis. GAPDH binds to AU-rich elements in the 3′ untranslated region of mRNA to suppress protein translation. That effect is relieved by increasing the abundance of glyceraldehyde-3-phosphate, the GAPDH substrate produced during glycolysis. Studies of T cells with transgenic expression of green fluorescent protein–linked GAPDH, isolated from mice infected with Listeria monocytogenes, show that the expression of IFN-γ and IL-2 protein is inversely correlated with GAPDH abundance. Interestingly, expression of the inhibitory molecule PD-1 is higher in T cells with higher expression of GAPDH. The authors suggest that the availability of glucose as a carbon source serves to regulate T cell effector function by influencing GAPDH activity as either a post-transcriptional regulator or a catalytic enzyme in the glycolysis pathway.

Cell 153, 1239–1251 (2013)