Fig. 3. Loss of TET2 limits terminal differentiation of exhausted CD8 T cells.

(A) Experiment schematic for RNA-seq and ATAC-seq. WT and TET2_KO P14 cells were analyzed at day 15 p.i. with LCMV clone 13. (B) Sorting strategy for T_EX subsets for RNA and ATAC-seq. (C and D) PCA of RNA-seq (C) and ATAC-seq (D) data for WT and TET2_KO T_EX subsets. (E and F) Number of DACRs (E) or DEGs (F) for each pairwise comparison between WT and TET2_KO T_EX subsets {FDR < 0.05, with variable absolute log₂ fold changes [abs(log₂FC)] indicated}. (G) Volcano plot highlighting DEG in WT compared to TET2_KO LY108^neg T_EX. (H) Example plots and data comparing expression of PD1, CD39, and 2B4 on TET2_KO LY108^neg T_EX to WT LY108^neg T_EX. (I) Correlation plot of differential gene expression and peak accessibility in TET2_KO LY108^neg T_EX compared to WT LY108^neg T_EX with TOX labelled. (J) Example tracks showing accessibility at the Tox locus in LY108^neg T_EX. Differentially Accessible Peaks (DAPs) are indicated in orange. (K and L) Example plots (K) and data (L) comparing TOX expression in TET2_KO LY108^neg T_EX to WT LY108^neg T_EX. [(H) and (L)] n = 9, spleen at day 30 p.i. with LCMV clone 13. Data for individual mice shown; representative of three independent experiments. ns P > 0.05; ****P < 0.0001 by paired t test. Schematic (A) created with BioRender.com.