T-cell exhaustion due to persistent antigen: quantity not quality?

T-cell exhaustion is characterized by failure to respond to a persistent antigen and is a hallmark of chronic infections and cancer. Here, we discuss several recent reports on T-cell exhaustion, including one in this issue of the European Journal of Immunology where Richter et al. [Eur. J. Immunol. 42:2290-2304] examine the importance of the amount of persistent antigen versus the cell type presenting it to induce CD8(+) T-cell exhaustion, and the consequences for host survival during chronic viral infection.