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

The longer-lived T_CM mainly reside in secondary lymphoid organs such as the lymph nodes, whereas the T_EM 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 T_CM might give rise to the more transient T_EM 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 T_CM proliferation response was more vigorous, perhaps because IL-7 (and IL-2) more efficiently activated the pro-survival factor STAT5 in T_CM.

Even without DCs, T_CM 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 T_CM increased FOXO3a phosphorylation at a particular residue, suggesting these cytokines might promote the long-term survival of T_CM by both increasing proliferation and decreasing death.