However, in the case of persistent HIV-1 infection, CD8+ T cells lose their functions in a hierarchical manner, successively impaired in producing IL-2, proliferating, delivering cytotoxic molecules like perforin and granzymes, producing TNF, IFN-γ, and MIP-1β, and finally attaining a so-called exhausted state (3). The gene discussed is CD8A; the disease is HIV-1 infection.