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

Miriam Podtschaske1, Uwe Benary, Sandra Zwinger

  • 1German Rheumatism Research Centre, Berlin, Germany.

Plos One
|September 27, 2007
PubMed

Insights

T-cell activation relies on interleukin-2 (IL-2) production. A novel NFATc2 molecular switch translates T-cell receptor (TCR) signal strength into the number of IL-2-producing T helper (Th) cells, regulating immune response participation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Interleukin-2 (IL-2) is crucial for T helper (Th) lymphocyte activation, influencing effector and regulatory T cell populations.
  • The strength of T cell receptor (TCR) stimulation dictates the frequency, not the amount, of IL-2 produced per cell.
  • IL-2 expression control is downstream of intracellular calcium levels, suggesting a molecular switch mechanism.

Purpose of the Study:

  • To elucidate the molecular mechanism translating TCR stimulation strength into IL-2 expression in Th cells.
  • To investigate the roles of NFATc2 and NF-kappaB in digital and graded signaling pathways.
  • To understand how these pathways regulate the number of IL-2-producing Th cells during immune responses.

Main Methods:

  • Analysis of NFATc2 and NF-kappaB activation in single Th cells following graded TCR stimulation.
  • Assessment of NFATc2 nuclear translocation dynamics.
  • Quantification of IL-2 transcription in relation to TCR signaling strength.

Main Results:

  • NFATc2 activation exhibits digital behavior, while NF-kappaB activation shows graded responses to TCR signaling.
  • NFATc2 nuclear translocation occurs in an all-or-none manner within individual cells.
  • The strength of TCR stimulation is converted into the number of nuclei positive for NFATc2 and IL-2 transcription.

Conclusions:

  • A digital NFATc2 switch mechanism regulates IL-2 expression in Th cells.
  • This switch translates graded TCR signals into a specific number of IL-2-producing cells.
  • The NFATc2 pathway controls the scale of Th cell participation in immune responses.

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