Fig. 5. TOX imposes a gene program of exhaustion in self-reactive CD8+ T cells.

10⁴ naive Tox^+/+ or Tox^−/− P14 cells were adoptively transferred into MOG-GP (a, c–f) and WT mice (b, e, f). One day later (day 0), mice were challenged i.c. with 10⁴ PFU rLCMV-GP33. Brain infiltrating P14 cells were FACS sorted for RNA-seq (a–f) and ATAC-seq (d) 21 days later. a Volcano plot of differentially expressed genes (DEGs) (FC ≥1.5; FDR ≤0.05) in Tox^+/+ vs. Tox^−/− A_L cells (n = 3 mice/group). b Volcano plot of differentially expressed genes (DEGs) (FC ≥1.5; FDR ≤0.05) in Tox^+/+ vs. Tox^−/− V_L cells (n = 3 mice/group). c GSEA of a signature of exhaustion and effector differentiation³³ in a ranked list of genes differentially expressed by Tox^+/+ vs. Tox^−/− A_L cells. NES: normalized enrichment score. d Diamond plot of differentially accessible ChARs adjacent to the top 50 up- and downregulated genes identified in (a). Top DEGs which possess at least one differential ChAR within a 15 kb distance are shown. Each diamond represents a ChAR assigned to a gene. Color code depicts the gain or loss of accessibility (Log₂ FC) in the comparison Tox^+/+ vs. Tox^−/− A_L cells. e Venn diagram showing the overlap of DEGs found in the comparisons Tox^+/+ vs. Tox^−/− in both A_L and V_L cells. f Enrichment of biological processes (GO terms) among the DEGs (up in Tox^+/+ vs. Tox^−/−) commonly or uniquely found in A_L and V_L cells. The top 10 most significantly enriched GO terms are shown for each category.