The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection.
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...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2000
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| _version_ | 1797057155104243712 |
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| author | Simon, A Auphan, N Pophillat, M Boyer, C Ghosh, S Rincón, M Flavell, R Schmitt-Verhulst, A |
| author_facet | Simon, A Auphan, N Pophillat, M Boyer, C Ghosh, S Rincón, M Flavell, R Schmitt-Verhulst, A |
| author_sort | Simon, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:32:14Z |
| format | Journal article |
| id | oxford-uuid:1dd740b8-9dac-49f3-91ee-60d3989d9a0d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:32:14Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:1dd740b8-9dac-49f3-91ee-60d3989d9a0d2022-03-26T11:13:11ZThe lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1dd740b8-9dac-49f3-91ee-60d3989d9a0dEnglishSymplectic Elements at Oxford2000Simon, AAuphan, NPophillat, MBoyer, CGhosh, SRincón, MFlavell, RSchmitt-Verhulst, ADeletion 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. |
| spellingShingle | Simon, A Auphan, N Pophillat, M Boyer, C Ghosh, S Rincón, M Flavell, R Schmitt-Verhulst, A The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection. |
| title | The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection. |
| title_full | The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection. |
| title_fullStr | The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection. |
| title_full_unstemmed | The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection. |
| title_short | The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection. |
| title_sort | lack of nf kappa b transactivation and pkc epsilon expression in cd4 cd8 thymocytes correlates with negative selection |
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