Fig. 5: HIF1α-glycolysis-driven AICD governs IFN-γ production in hypoxic T cells.
A Cell death of naïve WT CD4+ T cells activated under hypoxia for 3 days, with or without with 2-DG was measured by 7-AAD and Annexin V staining (N = 3 per group, ****p < 0.0001). B Cell death of naïve WT and Hif1α− / − CD4+ T cells activated under normoxia (21% O2) and hypoxia (1% O2) for 3 days was detected by 7-AAD/Annexin V staining (N = 6 per group, ****p < 0.0001). C, D Naïve WT and Hif1α− / − CD4+ T cells were activated under hypoxia, with z-VAD-fmk or without (DMSO); on day 3, cells were stained for 7-AAD and Annexin V to assess cell death (C) (N = 4 per group, ****p < 0.0001), and on Day 5, IFN-γ production was determined (D) (N = 4 per group, **p = 0.0016). E, F Naïve Hif1α− / − CD4+ T cells were activated under hypoxia, with or without 20 mM sodium acetate (NaAc) added on day 0; on Day 3, cells were stained for7-AAD and Annexin V to assess cell death (E) (N = 3 per group, ****p < 0.0001), and IFN-γ production was determined on Day 5 (F) (N = 6 per group, ****p < 0.0001). A two-sided Student’s t-test was used in (A, E and F) for statistical analyzes. Two-way ANOVA with Šídák’s multiple comparisons test (with adjustment) was used for (B–D). All the experiments were repeated at least twice. Pooled results shown in the dot plots depicted means ± SEM for all the samples in each group, with each dot denoting an independent sample. Source data were provided in the Source Data file.
