The transcription factor T-bet is expressed mainly in TEM cells.

A T cell transcription factor favors short-term benefits over long-term stability, according to a new study by Intlekofer et al. (page 2015).

Long-term protection against pathogens by CD8+ T cells is due to a self-renewing population of central memory (TCM) cells that circulate in the lymph nodes. When they see their target antigen, these cells first rapidly proliferate, become cytotoxic, and then head out to the periphery to fight the invaders. A faster attack mode is provided by effector memory T (TEM) cells, which are already in the periphery, but these cells quickly die out.

Memory T cell development requires a transcription factor called T-bet. Intlekofer et al. now find that mice lacking T-bet have plenty of TCM cells but lack the TEM pool. In normal mice, only the TEM cells expressed T-bet, suggesting that T-bet skews the balance between the two populations by driving the differentiation of activated CD8+ T cells into TEM cells.

CD8+ memory T cell development also requires signals from CD4+ T cells. The team found that these signals favored the growth of CD8+ TCM cells. Mice that lacked CD4+ T cells therefore had higher numbers of TEM cells than TCM cells. This expanded TEM population had high levels of T-bet protein. Deletion of T-bet corrected this defect by restoring the numbers of self-renewing cells.