Transcriptional and Epigenetic Control of Human Naive CD8+ T Cell Activation

The differentiation of CD8+ naive T cells into effector cells upon activation is essential for eliminating intracellular pathogens and cancerous cells, although the underlying epigenetic mechanisms remain incompletely characterized. By integrating multi-omics approaches, we systematically mapped chromatin remodeling dynamics and transcriptional networks during human CD8+ naive T cell activation. Comparative analysis revealed 568 and 541 genes with synchronized elevation in chromatin accessibility and transcription (dual-upregulated) at 24- and 72-hr post-activation, whereas 281 and 285 genes displayed coordinated suppression (dual-downregulated), relative to non-activated controls. Functional annotation of 24-hr upregulated genes identified enrichment in biological processes including apolipoprotein A-I binding, RNA binding, pyruvate metabolism and DNA damage responses. Protein-protein interaction network analysis identified key regulatory genes, including MCM10, RAD51, POLQ, LDHA, LINC01132, VDR, and EGR2, that are involved in these processes.