@misc{10481/94873,
year = {2004},
month = {2},
url = {https://hdl.handle.net/10481/94873},
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.},
publisher = {American Society for Biochemistry and Molecular Biology},
keywords = {Bcl-3},
keywords = {NFkappaB},
keywords = {Tolerant T cells},
title = {Bcl-3 and NFkappaB p50-p50 homodimers act as transcriptional repressors in tolerant CD4+ T cells},
doi = {10.1074/jbc.M312398200},
author = {Grundström, Susanna and Anderson, Per Olof and Scheipers, Peter and Sundstedt, Anette},
}