Specific CD8+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis

Figure 1 T cell exhaustion during diseases with persistent and high antigenemia. At the beginning of an infection, naïve T cells (T_N) are primed and differentiate into effector T cells (T_E). During acute infections, T_E are completely functional and control the pathogen/tumoural cell. After clearing the antigen, these cells are then deleted by apoptosis and a memory population is generated and maintained. Nevertheless, in conditions of chronic infections or tumours, these cells gradually loss their effector capacity, becoming exhausted. The greater the antigen load or duration of the infection, the more exhausted the cells become. The steps of exhaustion are summarised here. In “partial exhaustion I” IL-2 production, high expansion ability and ex vivo killing are lost. In “partial exhaustion II”, the more advanced stage of exhaustion, these cells lose their capacity to produce tumour necrosis factor (TNF)-α, produce less interferon-γ and proliferate less. In the final stage of exhaustion, these cells are deleted by apoptosis. Ag: Antigen; DD: Duration of the disease; EA: Expansion ability; IR: Inhibitory receptors’ expression.