Based on recent advances in techniques that can detect and enumerate antigen-specific CD8+ T cells, it is evident that these cells can differentially regulate CD8+ T cell effector mechanisms at the single-cell level. Interplay between effector mechanisms that are employed by antigen-specific CD8+ T cells during the immune response in vivo can be addressed with different techniques that "count" cells either directly (T cell receptor (TCR) expression) or indirectly (antigen-specific cytokine production).