病毒感染中CD8 T细胞衰竭的关键转录因子发掘

he phenomenon of CD8 T cell exhaustion, as a major challenge in the field of immunotherapy, seriously hinders the effective response of the immune system in dealing with chronic infections and cancers. To further explore the molecular mechanism of CD8 T cell exhaustion, we re-analyzed four publicly available bulk RNA-seq datasets and multiple single-cell RNA-seq datasets, and combined ATAC-seq and ChIP-seq data for epigenetic analysis. As a result of these studies, different CD8 T cell types were found out: There were differentially expressed gene clusters in naive T cells (Tna), effector T cells (Teff), memory T cells (Tmem) and exhausted T cells (Tex). Each cluster had unique expression pattern and was enriched in specific KEGG pathways, among which Tex cells significantly expressed inhibitory receptors. Pathway analysis further revealed the similarities of activation pathways between Teff and Tex cells and the differences between them and other cell types.Single-cell analysis identified key genes and their roles in the pseudotime, and epigenetic analysis showed that chromatin accessibility and histone modification changes correlated with cellular functional status. Transcription factor regulatory network was also constructed and key regulators of gene expression in Tex cells were identified. In addition, the effect of anti-PD-L1 treatment on CD8 T cells was investigated, and it was found to alter gene expression and exhausted subsets, reduce Tex-term cell numbers, and increase Tex-prog and Tex-eff numbers.