Bcl-3 and NF kappa B p50-p50 homodimers act as transcriptional repressors in tolerant CD4(+) 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

Additional file 3: Figure S3. of Small field dosimetry for the small animal radiotherapy research platform (SARRP)

Beam uniformity profile across the irradiated area for full set of therapeutic apertures. Beam profiles are presented for three different SSD at a depth of 0.15 mm in the phantom. Apertures sizes are: a) 5 × 5 mm, b) 3 × 3 mm, c) 3x9mm along x axis, d) 3x9mm along y axis, e) 1 mm diameter and f) 0.5 mm diameter. (PDF 326 kb

Additional file 1: Figure S1. of Small field dosimetry for the small animal radiotherapy research platform (SARRP)

Profiles for Dose Deposition for the entire range of therapeutic apertures for broad focus irradiation. Data was obtained using FilmQA Pro for 3 independent exposures for a) 31 cm SSD, b) 34 cm SSD and c) 38 cm SSD. Data is shown as average from 3 independent repeats ± standard error. (PDF 314 kb