Developmental control of antigen-induced thymic transcription factors

Antigen engagement of the TCR may lead to activation of mature T cells while inducing deletion or positive selection of immature thymocytes. Using thymocytes from TCR transgenic mice recognizing the allo-antigen H-2Kb we investigated whether double-positive CD4+ CD8+ (DP) thymocytes constitute a par...

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Bibliographic Details
Published in:International immunology 1996-09, Vol.8 (9), p.1421-1428
Main Authors: Simon, Anna Katharina, Auphan, Nathalie, Schmitt-Verhulst, Anne-Marie
Format: Article
Language:English
Subjects:
Animals
AP-1
Cyclosporine - pharmacology
DNA - metabolism
DNA-Binding Proteins - metabolism
Gene Expression Regulation, Developmental - drug effects
H-2 Antigens - immunology
Immunophenotyping
Ionomycin - pharmacology
Mice
Mice, Inbred CBA
Mice, Transgenic
NF-AT
NF-kappa B - metabolism
NF-kB
NFATC Transcription Factors
Nuclear Proteins
Protein Binding - drug effects
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - drug effects
T-Lymphocyte Subsets - immunology
Tetradecanoylphorbol Acetate - pharmacology
thymic selection
Thymus Gland - metabolism
Transcription Factor AP-1 - metabolism
Transcription Factors - metabolism
Transcription, Genetic
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Summary:Antigen engagement of the TCR may lead to activation of mature T cells while inducing deletion or positive selection of immature thymocytes. Using thymocytes from TCR transgenic mice recognizing the allo-antigen H-2Kb we investigated whether double-positive CD4+ CD8+ (DP) thymocytes constitute a particular developmental stage where signals originating from surface receptor engagement will lead to distinct nuclear signaling. We show that the developmental control of transcription factors is apparent, at least at two levels. First, NF-AT binding activity was not induced in response to either antigen or phorbol myristate acetate (PMA)/ionomycin in DP thymocytes, whereas it was induced in single-positive CD8 thymocytes. Second, antigen induced a different pattern of transcription factor binding activities than PMA/lonomycin in DP thymocytes, AP-1 activity being selectively induced by antigen and NF-kB by PMA/lonomycin. Further we show that the transcription factors found to be induced in the DP thymic population were not susceptible to the inhibitory effect of cyclosporin A.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/8.9.1421