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Expression and activation of T cell receptor dependent transcription factors in regulatory T cells

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T cell receptor signalling and therefore production of IL-2 upon antigen stimulation, has been shown to be impaired in regulatory T (Treg) cells. Whether the expression and activation of the major transcription factors NFATc2, AP-1 and Nf-κB are affected too, has not yet been determined. We found a strikingly lower expression of all three factors in human Treg cells compared to memory Th cells, but their activation was unharmed. Interestingly, after stimulation with PMA/Ionomycin, thus bypassing upstream signalling events, we found a small Treg cell subset, that was able to overcome its anergic phenotype and produced IL-2. This subpopulation is characterized by higher NFATc2, AP-1 and Nf-κB and lower FOXP3 levels compared to IL-2 nonproducing Treg cells. Our Data suggests that IL-2 production in Treg cells is not switched off by genetic imprinting, but rather the amounts and ratios of the essential transcription factors NFATc2, AP-1, Nf-κB and FOXP3 are essential to prevent IL-2 production in Treg cells and thereby suppport their anergic phenotype despite a very strong stimulation.

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Correspondence to H Bendfeldt.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Bendfeldt, H., Frischbutter, S., Kroeger, S. et al. Expression and activation of T cell receptor dependent transcription factors in regulatory T cells. Cell Commun Signal 7, A1 (2009) doi:10.1186/1478-811X-7-S1-A1

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Keywords

  • Cell Receptor
  • Treg Cell
  • Antigen Stimulation
  • Upstream Signalling
  • Strong Stimulation