For example, in chronic hepatitis caused by Hepatitis B Virus (HBV), effector CD8+ T cells show a multilayered “exhaustion” phenotype, with a markedly reduced proliferative capacity and the production of IFN-γ, IL-2, TNF-α, granzymes, or perforin (Hoogeveen et al., 2019), which may be associated with the upregulation of co-inhibitory receptors like programmed death 1(PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA) (Isogawa and Tanaka, 2015). The gene discussed is IFNG; the disease is chronic hepatitis.