In terms of epigenetic regulation, CR-B and CR-C were fully methylated in naive T cells that did not express PD-1, whereas during the differentiation of naive T cells to effector CD8+ T cells after viral infection, PD-1 expression levels were continuously upregulated and the methylation levels of these two regions gradually decreased, with a significant negative correlation between them (27). This evidence concerns the gene PDCD1 and viral infectious disease.