Thymocytes mature through several stages of development, defined by cell surface markers such as CD3, CD4, and CD8, in response to environmental cues. Signal transduction resulting from lymphocyte-stromal cell interactions is likely to activate inducible transcription factors which in turn govern stage-specific gene expression. In this report we show that inducible transcription factors such as AP-1 and NF-AT are constitutively nuclear, in response to intrathymic signals, in freshly isolated thymocytes at all stages of maturation. In CD4+CD8+ double positive (DP), but not in the more immature CD4-CD8- double negative (DN) thymocytes, constant stimulus from the thymic environment is required to maintain nuclear AP-1. Thus, disruption of the thymus and incubation of thymocytes at 37 degrees C downregulates DNA binding by nuclear factors AP-1 and NF-AT. Similar treatment of thymocytes has previously been shown to downregulate CD3 zeta chain phosphorylation and increase T cell receptor CD3 expression on DP thymocytes, which is a feature of repertoire selection. Since mature T cells maintain inducible nuclear factors in an inactive form until an encounter with antigen, we propose that downregulation of nuclear DNA binding proteins may reflect another feature of this stage of T cell maturation.
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December 01 1994
Nuclear factors that mediate intrathymic signals are developmentally regulated.
J Sen,
J Sen
Dana-Farber Cancer Institute, Boston, Massachusetts.
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Y Shinkai,
Y Shinkai
Dana-Farber Cancer Institute, Boston, Massachusetts.
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F W Alt,
F W Alt
Dana-Farber Cancer Institute, Boston, Massachusetts.
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R Sen,
R Sen
Dana-Farber Cancer Institute, Boston, Massachusetts.
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S J Burakoff
S J Burakoff
Dana-Farber Cancer Institute, Boston, Massachusetts.
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J Sen
Dana-Farber Cancer Institute, Boston, Massachusetts.
Y Shinkai
Dana-Farber Cancer Institute, Boston, Massachusetts.
F W Alt
Dana-Farber Cancer Institute, Boston, Massachusetts.
R Sen
Dana-Farber Cancer Institute, Boston, Massachusetts.
S J Burakoff
Dana-Farber Cancer Institute, Boston, Massachusetts.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 180 (6): 2321–2327.
Citation
J Sen, Y Shinkai, F W Alt, R Sen, S J Burakoff; Nuclear factors that mediate intrathymic signals are developmentally regulated.. J Exp Med 1 December 1994; 180 (6): 2321–2327. doi: https://doi.org/10.1084/jem.180.6.2321
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