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Correlating notch signaling with thymocyte maturation

M L Deftos1, Y W He, E W Ojala

  • 1Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.

Immunity
|January 9, 1999
PubMed

Insights

Notch signaling, crucial for T cell development, was found to make thymomas resistant to apoptosis. This pathway also promotes the maturation of double-positive (DP) thymocytes into CD4+ and CD8+ single-positive (SP) T cells.

Area of Science:

  • Immunology
  • Developmental Biology
  • Molecular Biology

Background:

  • The Notch receptor and its ligands play vital roles in numerous developmental processes.
  • Notch signaling is highly expressed in the thymus and implicated in the CD4/CD8 lineage decision during T cell development.

Purpose of the Study:

  • To investigate the role of Notch-1 signaling in thymocyte maturation and steroid resistance.
  • To determine if activated Notch-1 can influence glucocorticoid-induced apoptosis in T cells.

Main Methods:

  • Identification of the constitutively active intracellular fragment of murine Notch-1.
  • Testing the effect of activated Notch-1 on thymomas, T cell lines, and CD4+ CD8+ DP thymocytes.
  • Analysis of marker upregulation associated with DP maturation.

Main Results:

  • Constitutively active Notch-1 rendered thymomas resistant to glucocorticoid-induced apoptosis.
  • This steroid resistance effect was confirmed in various T cell lines and primary DP thymocytes.
  • Activation of Notch signaling upregulated markers correlated with DP maturation into CD4 and CD8 lineages.

Conclusions:

  • Notch signaling is critically involved in the maturation of double-positive (DP) thymocytes.
  • The Notch pathway influences the differentiation of DP thymocytes into both CD4+ and CD8+ single-positive (SP) T cells.
  • Notch signaling confers resistance to steroid-induced apoptosis, a characteristic associated with DP maturation.

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