The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection

Tools

Item Type:	Article
Title:	The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection
Creators Name:	Simon, A.K., Auphan, N., Pophillat, M., Boyer, C., Ghosh, S., Rincón, M., Flavell, R.A. and Schmitt-Verhulst, A.M.
Abstract:	Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens. In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen. Using triple transgenic mice expressing a TCR transgene, dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites, we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes, whereas both were transcriptionally active in mature T cells after antigenic stimulation. Lack of NF-kappa B induction correlated with increased death in response to antigen. AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes. In contrast, we found a complete lack of constitutive expression of the epsilon isoform of Protein Kinase C (PKC) in DP thymocytes, although it was present in mature thymocytes and peripheral T cells. Taken together the results suggest that the lack of PKC epsilon in DP thymocytes could lead to the absence of NF-kappa B activity after antigenic stimulation contributing to negative selection. Cell Death and Differentiation (2000) 7, 1253 - 1262.
Keywords:	CD4+ CD8+ Thymocytes, NF-kB, PKCe, ras/Mek, Thymic Death, AP-1, Animals, Mice
Source:	Cell Death and Differentiation
ISSN:	1350-9047
Publisher:	Nature Publishing Group
Volume:	7
Number:	12
Page Range:	1253-62
Date:	1 December 2000
Official Publication:	https://doi.org/10.1038/sj.cdd.4400760
PubMed:	View item in PubMed

Repository Staff Only: item control page