Activation-induced non-responsiveness (anergy) limits CD8 T cell responses to tumors.

Naïve CD8 T cells respond to signals provided by Ag, costimulation and cytokines by proliferating and differentiating to develop effector functions. Following initial clonal expansion, however, the cells develop activation-induced non-responsiveness (AINR), a form of anergy characterized by an inability to produce IL-2. Cells in the AINR state can carry out effector functions (cytolysis, IFN-gamma production) but cannot continue to proliferate and expand in the face of persisting Ag. AINR limits the ability of activated CTL to control tumor growth but can be reversed by IL-2, provided either therapeutically or by activated CD4 T helper cells, to allow continued expansion.