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 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)/lonomycin 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-kappa B 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.
Simon
A K
AK
Centre d'Immunologie INSERM-CNRS de Marseille Luminy, Parc Scientifique de Luminy, France.
Auphan
N
N
Schmitt-Verhulst
A M
AM
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006183:H-2 Antigens / Q000276:immunology*; D016130:Immunophenotyping; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011485:Protein Binding / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D015759:Ionomycin; D016572:Cyclosporine; D004247:DNA; D013755:Tetradecanoylphorbol Acetate