Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression

Abstract

The expression of Interleukin-2 (IL-2) is a key event in T helper (Th) lymphocyte activation, controlling both, the expansion and differentiation of effector Th cells as well as the activation of regulatory T cells. We demonstrate that the strength of TCR stimulation is translated into the frequency of memory Th cells expressing IL-2 but not into the amount of IL-2 per cell. This molecular switch decision for IL-2 expression per cell is located downstream of the cytosolic Ca2+ level. Here we show that in a single activated Th cell, NFATc2 activation is digital but NF-KB activation is graded after graded T cell receptor (TCR) signaling. Subsequently, NFATc2 translocates into the nucleus in an-all-or-none fashion per cell, transforming the strength of TCR-stimulation into the number of nuclei positive for NFATc2 anil IL-2-transcription. Thus, the described NFATc2 switch regulates the number of Th cells actively participating in an immune response. © 2007 Podtschaske et al.