Fig. 4.

FXR regulates the metabolism of effector CD8⁺ T cells. (A–F) Bioenergetic profiling of wild type (T^WT) and T^ΔFXR effector CD8⁺ T cells. Extracellular flux measurements were carried out in the presence of glucose (11 mM) and L-glutamine (2 mM). (A and B) T^WT and T^ΔFXR mice were infected with LCMV Armstrong. Mice were fed ad libitum or fasted for 24 h on D5 post infection as described in Fig. 1B. CD8⁺ effector T cells were FACS-purified at the end of the fasting. (A) Baseline OCR. (B–E) Mitochondrial fuel utilization showing changes in OCR over time in response to the mitochondrial pyruvate carrier inhibitor UK5099 (2 μM), the CPT1 inhibitor etomoxir (Eto, 4 μM), or the glutaminase inhibitor BPTES (3 μM). (D–F) Naive CD8⁺ T cells were activated in vitro with CD3/CD28 beads in the presence of IL-2 for 3 d to generate effector cells (D and E). Contribution of indicated fuels to mitochondrial respiration. Data in E are plotted as the percentage of basal OCR after injection of inhibitor. (F) In-vitro–generated effector cells were exposed to various concentrations of glucose in the presence or absence of glutamine for 24 h. Cell survival was determined by FACS. Data are plotted as mean ± SD (n = 3 to 11), representative of at least two independent experiments. Statistical significance determined by one- or two-way ANOVA followed by a Dunnet (A), Sidak (E), or Tukey (F) correction for multiple comparisons. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.