Thus, the 4-1BB capability of discriminating between low and high antigen-specific CD4+ T-cell-mediated IFN-γ responses could be instrumental to find novel strategies based on T cells and co-stimulatory signals to down-regulate the effects of elevated antigen-specific IFN-γ responses associated with TB pathology and its negative impact on vaccine protection. The gene discussed is CD4; the disease is tuberculosis.