Chronic Virus Infection Enforces Demethylation of the Locus that Encodes PD-1 in Antigen-Specific CD8+ T Cells

摘要: Summary Functionally exhausted T cells have high expression of the PD-1 inhibitory receptor, and therapies that block signaling show promise for resolving chronic viral infections cancer. By using human murine systems acute infections, we analyzed epigenetic regulation during CD8 + T cell differentiation. During infection, naive to effector differentiation was accompanied by a transient loss DNA methylation Pdcd1 locus directly coupled duration strength receptor signaling. Further into functional memory cells coincided with remethylation, providing an adapted program expression. In contrast, regulatory region completely demethylated in remained unmethylated even when virus titers decreased. This lack remethylation leaves poised rapid expression, potentially signal premature termination antiviral functions.