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

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...

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Main Authors: Miriam Podtschaske, Uwe Benary, Sandra Zwinger, Thomas Höfer, Andreas Radbruch, Ria Baumgrass
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-09-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0000935
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author Miriam Podtschaske
Uwe Benary
Sandra Zwinger
Thomas Höfer
Andreas Radbruch
Ria Baumgrass
author_facet Miriam Podtschaske
Uwe Benary
Sandra Zwinger
Thomas Höfer
Andreas Radbruch
Ria Baumgrass
author_sort Miriam Podtschaske
collection DOAJ
description 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.
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spelling doaj.art-c146b7498b194d678b9ec4d15b08291e2022-12-21T18:40:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-09-0129e93510.1371/journal.pone.0000935Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.Miriam PodtschaskeUwe BenarySandra ZwingerThomas HöferAndreas RadbruchRia BaumgrassThe 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.https://doi.org/10.1371/journal.pone.0000935
spellingShingle Miriam Podtschaske
Uwe Benary
Sandra Zwinger
Thomas Höfer
Andreas Radbruch
Ria Baumgrass
Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
PLoS ONE
title Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
title_full Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
title_fullStr Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
title_full_unstemmed Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
title_short Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
title_sort digital nfatc2 activation per cell transforms graded t cell receptor activation into an all or none il 2 expression
url https://doi.org/10.1371/journal.pone.0000935
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