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. Author manuscript; available in PMC: 2022 Jan 26.
Published in final edited form as: Nat Immunol. 2021 Jul 26;22(8):1030–1041. doi: 10.1038/s41590-021-00982-6

Figure 6: Transcriptional analysis confirms broad changes in TEX after removal of antigen, but also identifies exhaustion scars in the transcriptional landscape.

Figure 6:

HCV-specific MHC-multimer-sorted CD8+ T cells from patients pre- and post-DAA treatment were compared with those from patients who resolved infection spontaneously. a, b, Venn diagrams showing the number of differentially expressed genes (DEGs) and overlap between TEX pre- vs post-DAA therapy (paired samples, n=6), vs TMEM from resolver patients (n=8) (a), or vs TESC (paired samples n=6) (b). c, Principal component analysis of gene expression profiles from pre-DAA TEX, post-DAA TEX, and resolver TMEM cells. d, Gene set enrichment analysis (GSEA) of the transcriptional signature “reactome PD1 signaling (C2)” and “up in effector vs memory CD8+ T cell (C7)” enriched in pre-DAA TEX cells compared post-DAA (left panel) or in pre-DAA TESC cells compared post-DAA (right panel). e, GSEA of transcriptional signature “reactome translation (C2)” and “down in KLRG1 high vs low effector CD8+ T cells (C7)” enriched negatively in resolver TMEM cells compared to post-DAA TEX cells (left panel) or in pre-DAA TESC cells compared to post-DAA (right panel). f, Plot showing the log2 fold change difference of transcription factors and cofactors between post-DAA TEX and resolver T cells with respect to pre-DAA TEX cells. Transcription factors and cofactors that did not recover are highlighted in yellow font and with a red frame if statistical validation was made on 9 additional TEX populations post-DAA therapy and compared to TMEM (Extended Data Fig. 6c). g, Expression (log2 counts) of TOX, TCF7, ETV1 and NKX3–1 in TEX and TESC pre- and post-DAA (paired samples n=6) as well as in resolver TMEM cells (n=8). Box plots show the median (vertical bar), 25th and 75th percentiles (lower and upper bounds of the box, respectively) and 1.5 times the interquartile range (or minimum/maximum values if they fall within that range; end of whiskers). Statistical testing by moderated t-test (two-sided, unadjusted).