Does programmed CTL proliferation optimize virus control?

CD8 T-cell or cytotoxic T-lymphocyte responses develop through an antigen-independent proliferation and differentiation program. This is in contrast to the previous thinking, which was that continuous antigenic stimulation was required. This Opinion discusses why nature has chosen the proliferation program and how it compares to continuous stimulation. Although the two mechanisms should not lead to significantly different dynamics during chronic infection, they do make a difference in acute infection. We argue that programmed proliferation is better at clearance, whereas continuous stimulation is better at limiting acute symptoms. The 7–10 programmed cell divisions observed in vivo might be an optimization of this trade-off. We also discuss the conditions under which the program does or does not require CD4 T-cell help for clearance.