Fig. 4: VHL expression in lung CD4 T cells from M. tuberculosis-infected mice controls proliferation and effector responses.

RNA seq was performed in Vhl cKO (n = 6) and WT (n = 5) CD4 T cells isolated from the lungs of M. tuberculosis-infected mice. a MA plot in which each point represents a gene. The plot illustrates the change of expression (y axis, log₂ fold change) and the average transcript abundance over all samples (x axis, log₂ counts per million). Colors indicate the significantly upregulated (in red) or down-regulated (in light blue) in Vhl cKO as compared to WT CD4 T cells. The top 25 most significant genes are indicated by their gene symbols. b In the heat map the log₂ counts for each gene (row) is standardized to mean = 0, and the differences with the mean depicted. c Umap dimensionality reduction plots from non-supervised samples based on the normalized gene counts after filtering the low expressed genes. There are 2 outliers in the Vhl cKO CD4 T cell group, probably explained by their lower sample weight. d, e The log₁₀ p value of the enrichment of hallmark gene sets in the transcriptome of Vhl cKO (d) and WT (e) CD4 T cells was compared using the MSigDB databases. f–h The heat maps of selected RNA-seq data showing: HIF-pathway-specific genes (f), genes involved in T cell exhaustion or dysfunction (g), and MYC-regulated transcripts (h). Data were normalized by subtracting the log₂ transformed values to the mean log₂ value for all samples for each gene. i, j Lung cell suspensions were labeled with mitochondrial-selective MitoTracker Green to assess mitochondrial mass and Mito Tracker Red to measure mitochondrial ROS. The MFI of Mito Tracker green, to assess mitochondrial mass (i), and Mito SOX Red, to assess mitochondrial ROS, (j) labeled live CD4 and CD8 T cells from the lung of Vhl cKO and WT mice (n = 6 per group) 8 weeks after infection with M. tuberculosis are shown. i, j Each symbol represents one mouse, and the data are presented as the mean ± s.e.m. d–j The p values were calculated using a two-tailed unpaired t test with Welch’s correction (k, m) and FDR adjustment for multiple comparisons (d–h). Source data are provided as a Source Data file.