Bcl-3 and NFkappaB p50-p50 homodimers act as transcriptional repressors in tolerant CD4+ T cells Grundström, Susanna Anderson, Per Olof Scheipers, Peter Sundstedt, Anette Bcl-3 NFkappaB Tolerant T cells 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. 2024-09-23T09:50:45Z 2024-09-23T09:50:45Z 2004-02 journal article Grundström, Susanna et al. “Bcl-3 and NFkappaB p50-p50 homodimers act as transcriptional repressors in tolerant CD4+ T cells.” The Journal of biological chemistry vol. 279,9 (2004): 8460-8. doi:10.1074/jbc.M312398200 https://hdl.handle.net/10481/94873 10.1074/jbc.M312398200 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional American Society for Biochemistry and Molecular Biology