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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
07:48

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist

Published on: April 25, 2018

T cell receptor-induced activation and apoptosis in cycling human T cells occur throughout the cell cycle

M Karas1, T Z Zaks, J L Liu

  • 1Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1770, USA. karas@box-k.nih.gov

Molecular Biology of the Cell
|December 10, 1999
PubMed

Insights

T cell activation and apoptosis can occur in any cell cycle phase. This study used centrifugal elutriation to avoid toxic agents, finding no cell cycle specificity for T cell receptor activation or cell death.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Conflicting data exists on T cell susceptibility to activation-induced cell death (AICD) across the cell cycle.
  • Previous synchronization methods used toxic pharmacological agents, potentially confounding results.

Purpose of the Study:

  • To investigate the relationship between T cell cycle phases and activation-induced cell death.
  • To determine if T cell activation and apoptosis are restricted to specific cell cycle phases using non-toxic methods.

Main Methods:

  • Human T cell lines (melanoma-reactive, CD8+ HER-2/neu-reactive, Jurkat) were synchronized using centrifugal elutriation.
  • Cell cycle fractions (G0-G1, S, G2-M) were analyzed for T cell receptor (TCR)-mediated activation (intracellular Ca2+ flux, cytolytic activity, Fas ligand mRNA).
  • Susceptibility to Fas ligand-induced apoptosis and AICD was assessed across cell cycle phases.

Main Results:

  • TCR-mediated activation markers were detected in all cell cycle phases (G0-G1, S, G2-M).
  • Cytolytic recognition and Fas ligand mRNA induction occurred irrespective of the cell cycle phase.
  • Susceptibility to both Fas ligand-induced apoptosis and AICD was not confined to any specific cell cycle phase.

Conclusions:

  • In non-transformed human T cells, T cell receptor (TCR) activation and subsequent apoptosis can occur throughout all phases of the cell cycle.
  • Centrifugal elutriation provides a non-toxic method for cell cycle synchronization, yielding reliable data on T cell activation and death pathways.
  • The findings resolve previous discrepancies by demonstrating cell cycle-independent T cell activation and apoptosis.

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