In the brains of PD-L1−/− mice a number of upstream regulators were enriched during acute infection but reduced or below threshold during persistent infection (e.g., IFN-γ, IL-15, NOS, NFATC2, and IL12-A), suggesting dynamic epigenetic changes in these genes in the absence of PD-1 signaling. The gene discussed is PDCD1; the disease is infection.