AI Article Synopsis

  • The study investigates how tolerant T cells fail to produce interleukin (IL)-2, focusing on the regulation of NFkappaB-mediated transcription.
  • A key finding is that tolerant T cells show a predominance of p50-p50 homodimers binding to the IL-2 promoter, which correlates with repressed NFkappaB-driven transcription.
  • Additionally, the impaired movement of the p65 subunit and high levels of the p50 protein in these cells point to complex regulatory mechanisms affecting IL-2 production in tolerant CD4(+) T cells.

Article Abstract

The transcriptional events that control T cell tolerance are still poorly understood. To investigate why tolerant T cells fail to produce interleukin (IL)-2, we analyzed the regulation of NFkappaB-mediated transcription in CD4(+) T cells after tolerance induction in vivo. We demonstrate that a predominance of p50-p50 homodimers binding to the IL-2 promoter kappaB site in tolerant T cells correlated with repression of NFkappaB-driven transcription. Impaired translocation of the p65 subunit in tolerant T cells was a result from reduced activation of IkappaB kinase and poor phosphorylation and degradation of cytosolic IkappaBs. Moreover, tolerant T cells expressed high amounts of the p50 protein. However, the increased expression of p50 could not be explained by activation-induced de novo synthesis of the precursor p105, which was constitutively expressed in tolerant T cells. We also demonstrate the exclusive induction of the IkappaB protein B cell lymphoma 3 (Bcl-3) in tolerant T cells as well as its specific binding to the NFkappaB site. These results suggest that the cellular ratio of NFkappaB dimers, and thus the repression of NFkappaB activity and IL-2 production, are regulated at several levels in tolerant CD4(+) T cells in vivo.

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Source
http://dx.doi.org/10.1074/jbc.M312398200DOI Listing

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