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Related Experiment Videos

Helper T cell differentiation is controlled by the cell cycle

J J Bird1, D R Brown, A C Mullen

  • 1Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, IL 60637, USA.

Immunity
|September 5, 1998
PubMed
Summary
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Helper T cell differentiation relies on cell division and cytokine signals. Epigenetic changes during cell cycles control gene expression, ensuring stable T helper cell fate.

Area of Science:

  • Immunology
  • Cell Biology
  • Epigenetics

Background:

  • Helper T (Th) cell differentiation is crucial for adaptive immunity.
  • Cytokines and mitogens are known regulators of Th cell differentiation.
  • The interplay between cell proliferation and differentiation remains incompletely understood.

Purpose of the Study:

  • To delineate the relationship between cell proliferation and differentiation in Helper T cells.
  • To understand the role of cell cycle progression in regulating cytokine gene expression.
  • To investigate the epigenetic mechanisms governing Th cell fate determination.

Main Methods:

  • Analysis of gene expression in discrete generations of dividing Th cells.
  • Assessment of cell cycle-dependent and independent cytokine expression (IL-2, IFN-gamma, IL-4).

Related Experiment Videos

  • Investigation of epigenetic modifications (histone acetylation, DNA demethylation) during differentiation.

    • Main Results:

    • Initial IL-2 expression is cell cycle-independent, while effector cytokine expression is cell cycle-dependent.
    • IFN-gamma expression frequency increases with cell cycles; IL-4 requires three divisions.
    • Cell cycle progression and cytokine signaling cooperate to overcome epigenetic repression.
    • Terminally differentiated cells show stable, cell cycle-independent gene expression due to epigenetic modifications.

    Conclusions:

    • Th cell fate is governed by a novel mechanism integrating proliferative and differentiative signals.
    • Epigenetic modifications established during cell cycling maintain the stability of the differentiated state.
    • Understanding this process offers insights into immune regulation and potential therapeutic targets.