Extended Data Fig. 5: ETV7 increases functional exhaustion of CD8+ T cells during infection in mice and humans.
a-c, Related to Extended Data Fig. 4e. Naïve CD45.1 P14 CD8+ T cells were enriched from P14 mice and transfected with lentivirus expressing ETV7 or vector control. The cells were then adoptively transferred into CD45.2 host mice. After infusion, mice were infected with Armstrong. CD45.1 P14 CD8+ T cells from the spleen were analyzed on days 0 to 22 post infection. GP33 tetramer+CD45.1+ cells (a) and cytokine expression (IFNγ and TNFα) (b) were analyzed by FACS after infected by Armstrong. Viral load in spleen were detected by RT-PCR according to previous protocol127 (c). n = 4 mice per group. The experiment was independently repeated three times with similar results. d, Naïve CD45.1 P14 CD8+ T cells were enriched from P14 mice and transfected with lentivirus expressing ETV7 or vector control. The cells were then adoptively transferred into CD45.2 host mice. After infusion, mice were infected with Clone 13. TCF1 + TIM3−CD8+ T cells and TCF1−TIM3+CD8+ T cells were analyzed by FACS (n = 4 mice per group). The experiment was independently repeated three times with similar results. e, f, UMAP visualization showing the level of memory score (left panel), exhaustion score (middle panel), and expression level of ETV7 (right panel) in CD8+ T cell clusters from scRNA-seq datasets of COVID-19 infected patients (e). Correlation between the mean expression level of ETV7 and mean memory score (left panel) or exhaustion score (right panel) in all CD8+ T cells from scRNA-seq datasets of COVID-19 infected patients (f). P-values were calculated using Pearson correlation analysis and are indicated. All data are the mean ± SD. Significance was calculated by two-sided unpaired Student’s t-test.
