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

PLoS One. 2007 Sep 26;2(9):e935. doi: 10.1371/journal.pone.0000935.

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-kappaB 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 and IL-2 transcription. Thus, the described NFATc2 switch regulates the number of Th cells actively participating in an immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Calcineurin / pharmacology
  • Calcium / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Flow Cytometry
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Ionomycin / pharmacology
  • Lectins, C-Type
  • Lymphocyte Activation / drug effects
  • Models, Theoretical
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • Phosphorylation
  • Receptors, Antigen, T-Cell / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / metabolism*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Interleukin-2
  • Lectins, C-Type
  • NF-kappa B
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • Receptors, Antigen, T-Cell
  • Ionomycin
  • Interferon-gamma
  • Calcineurin
  • Calcium