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T cell memory is a cornerstone of protective immunity, and is the key element in successful vaccination. Upon encountering the relevant pathogen, memory T cells are thought to initiate cell division much more rapidly than their naïve counterparts, and this is thought to confer a significant biological advantage upon an immune host. Here, we use traceable TCR-transgenic T cells to evaluate this proposed characteristic in CD4 +  and CD8 +  memory T cells. We find that, even in the presence of abundant antigen that was sufficient to induce  in vivo  IFNγ production by memory T cells, both memory and naïve T cells show an extended, and indistinguishable, delay in the onset of proliferation. Although memory cells can detect, and respond to, virus infection within a few hours, their proliferation did not begin until ∼3 days after infection, and occurred simultaneously in all anatomical compartments. Thereafter, cell division was extraordinarily rapid for both naïve and memory cells, with the latter showing a somewhat accelerated accumulation. We propose that, by permitting memory T cells to rapidly exert their effector functions while delaying the onset of their proliferation, evolution has provided a safeguard that balances the risk of infection against the consequences of severe T cell–mediated immunopathology.

Tentative T Cells: Memory Cells Are Quick to Respond, but Slow to Divide