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Related Experiment Videos

p27Kip1 regulates T cell proliferation.

S Mohapatra1, D Agrawal, W J Pledger

  • 1Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Department of Oncology, Department of Biochemistry, University of South Florida College of Medicine, Tampa, Florida 33612, USA.

The Journal of Biological Chemistry
|April 12, 2001
PubMed
Summary

Serum and T cell receptor (TCR) agonists are crucial for T cell proliferation. Serum enhances T cell activation by regulating the cyclin-dependent kinase 2 (cdk2) inhibitor p27(Kip1), promoting cell cycle entry.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell proliferation is essential for adaptive immunity.
  • Serum and T cell receptor (TCR) agonists are known to stimulate T cells.
  • The precise mechanisms underlying serum-dependent T cell activation remain incompletely understood.

Purpose of the Study:

  • To elucidate the mechanism by which serum promotes T cell proliferation in conjunction with TCR agonists.
  • To investigate the role of specific cell cycle regulators in serum-dependent T cell activation.

Main Methods:

  • Primary splenic T cells were stimulated with TCR agonists in the presence or absence of serum.
  • Cell cycle progression was monitored, and the activation status of cyclin-cdk complexes was assessed.

Related Experiment Videos

  • The expression and localization of the cdk2 inhibitor p27(Kip1) were analyzed.
  • Experiments were conducted using both wild-type and p27(Kip1)-null splenocytes.

    • Main Results:

    • TCR agonists alone induced G(0)/G(1) phase transition and cyclin D3-cdk6 activation, independent of serum.
    • Both TCR agonists and serum were required for cyclin E-cdk2 and cyclin A-cdk2 activation, and subsequent S phase entry.
    • Serum enhanced cdk2 activation by prolonging the TCR-induced downregulation of p27(Kip1).
    • Absence of p27(Kip1) rendered T cells independent of serum for cdk2 activation and S phase entry.

    Conclusions:

    • Serum is critical for T cell proliferation by facilitating cdk2 activation through sustained reduction of p27(Kip1).
    • The findings provide a mechanistic explanation for the serum dependence of T cell mitogenesis.
    • p27(Kip1) is a key mediator of serum's effect on T cell cycle progression.