Both stable and unstable interactions between T cells and antigen-presenting cells (APCs) have been observed in vivo, but the functional importance of these two types of contacts for T cells activation remains unclear. In Immunity, Marangoni et al. show that transient versus sustained T cell–APC interactions can be 'translated' into differences in gene activation in a manner dependent on the protracted nuclear retention of NFAT transcription factors. Contact of CD8+ T cells with APCs induces fast accumulation of NFAT in the nucleus (half-life, ∼1 min), whereas export of NFAT from the nucleus is slow (half-life, ∼20 min). During that 'signal memory' phase, NFAT remains transcriptionally active for the tolerance-associated gene Egr2 but not for the effector cytokine–encoding gene Ifng, which requires active signaling via the TCR for expression. As regulatory T cells can impair stable contacts between effector T cells and APCs, unstable interactions and retention of NFAT in the nucleus may represent a mechanism for inducing tolerance.

Immunity (10 January 2013) http://dx.doi.org/10.1016/j.immuni.2012.09.012