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Expression of activated CDC42 induces T cell apoptosis in thymus and peripheral lymph organs via different pathways

S Na1, B Li, I S Grewal

  • 1Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, CT 06520-8011, USA.

Oncogene
|January 19, 2000
PubMed

Insights

Activated CDC42 protein in transgenic mice causes thymocyte and T cell apoptosis, leading to reduced T cell populations. Apoptosis pathways differ between thymus and peripheral T cells, with Fas dependence varying.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CDC42 is a Ras-related GTP binding protein crucial for lymphocyte functions.
  • Dysregulation of CDC42 can impact immune cell development and homeostasis.

Purpose of the Study:

  • To investigate the role of constitutively active CDC42 in T cell development and apoptosis.
  • To elucidate the specific apoptotic pathways triggered by activated CDC42 in different T cell compartments.

Main Methods:

  • Generation of transgenic mice expressing constitutively active murine CDC42 (Q61L) under the CD2 promoter.
  • Flow cytometry analysis of thymocyte and peripheral T cell populations.
  • Assessment of apoptosis markers, including Fas and Fas ligand expression.

Main Results:

  • Transgenic mice exhibited smaller thymi with reduced CD4+CD8+, CD4+, and CD8+ thymocytes, and an increase in CD4-CD8- thymocytes.
  • High levels of thymocyte apoptosis were observed, contributing to reduced thymus cellularity.
  • Mature T cells in peripheral organs were significantly reduced and underwent massive apoptosis.
  • Apoptosis in thymocytes was Fas-independent, while peripheral T cell apoptosis was Fas-dependent.

Conclusions:

  • Constitutively active CDC42 induces distinct apoptotic pathways in thymocytes and peripheral T cells.
  • Activated CDC42 plays a critical role in regulating T cell survival and development.
  • Fas-mediated apoptosis is differentially involved in T cell loss in the thymus versus peripheral lymphoid organs.

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