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Molecular basis for developmental changes in interleukin-2 gene inducibility

D Chen1, E V Rothenberg

  • 1Division of Biology, California Institute of Technology, Pasadena 91125.

Molecular and Cellular Biology
|January 1, 1993
PubMed
Summary

Interleukin-2 (IL-2) gene expression in developing T cells changes during intrathymic selection. Specific DNA-binding factors, NF-AT and AP-1, are key to these IL-2 inducibility changes during T cell maturation.

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Specific regulation of fos family transcription factors in thymocytes at two developmental checkpoints.

International immunology·1999

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Development

Background:

  • Intrathymic T-cell development involves distinct stages marked by the ability to express the interleukin-2 (IL-2) gene.
  • IL-2 gene inducibility is acquired early, lost during selection, and regained in mature thymocytes.
  • Understanding the regulation of IL-2 gene expression is crucial for deciphering T-cell development.

Purpose of the Study:

  • To investigate the role of DNA-binding proteins in regulating IL-2 gene expression during T-cell development.
  • To identify molecular mechanisms underlying changes in IL-2 inducibility across thymocyte subsets.
  • To correlate specific transcription factor activities with thymocyte selection stages.

Main Methods:

  • Analysis of DNA-binding protein representation in different thymocyte subsets.

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  • Stimulation of cells with calcium ionophore A23187 and phorbol ester to assess inducible DNA-binding activities.
  • Classification of factors based on their activation patterns in various thymocyte populations.

    • Main Results:

    • DNA-binding proteins were categorized into four classes: constitutive (Oct-1, Sp1), broadly inducible (NF-kappa B, CD28-responsive elements), selection-sensitive inducible (NF-AT, AP-1), and culture-inducible (CREB).
    • NF-AT and AP-1 activities were abrogated in thymocytes undergoing positive and negative selection (CD4+ CD8+ TcRlow).
    • Constitutive factors were present throughout development, while NF-kappa B and CD28-responsive element binders were activated in all stages, including selection.

    Conclusions:

    • Inducible transcription factors are dynamically regulated during intrathymic T-cell development.
    • NF-AT and AP-1 are identified as key factors sensitive to developmental changes during thymocyte selection.
    • These findings provide a molecular basis for understanding how selection processes influence T-cell maturation and IL-2 gene regulation.