IL-2– and IL-7–induced phosphorylation of FOXO3a (top) may promote survival of TCM.

T cells that remember a previously encountered virus are essential in establishing protective immunity. But some T cells have a longer lifetime, and thus effectively a longer immunological memory, than others. Work by Riou et al. (page 79) might explain why effector memory T cells (TEM) are short lived, whereas central memory T cells (TCM) are maintained in the body long-term.

The longer-lived TCM mainly reside in secondary lymphoid organs such as the lymph nodes, whereas the TEM are found in the peripheral tissues and sites of infection. The exact ontogeny of the two cell types is unknown, but it's thought that TCM might give rise to the more transient TEM fighters. Regardless of origin, the biological basis for their different life spans was unknown.

Dendritic cells (DCs) were a good starting point, as they are known to produce the T cell survival factor IL-7. The team added dendritic cells to the two memory cell populations and found that the TCM proliferation response was more vigorous, perhaps because IL-7 (and IL-2) more efficiently activated the pro-survival factor STAT5 in TCM.

Even without DCs, TCM were less susceptible to apoptosis. These cells had less active pro-apoptotic transcription factor FOXO3a and lower transcription of its targets. FOXO3a activity is inhibited by phosphorylation, and adding IL-7 or IL-2 to the TCM increased FOXO3a phosphorylation at a particular residue, suggesting these cytokines might promote the long-term survival of TCM by both increasing proliferation and decreasing death.