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Glucocorticoids regulate TCR-induced elevation of CD4: functional implications.

G J Wiegers1, I E Stec, W E Klinkert

  • 1Section of Neuroimmunoendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.

Journal of Immunology (Baltimore, Md. : 1950)
|June 8, 2000
PubMed
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T cell activation increases CD4 expression, enhancing T cell sensitivity. Glucocorticoids like corticosterone accelerate this CD4 upregulation, boosting T cell proliferation and potentially impacting HIV entry.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • CD4 is a crucial coreceptor for T cell receptor (TCR)-mediated antigen recognition.
  • TCR engagement with MHC class II molecules significantly enhances T cell sensitivity to antigens.

Purpose of the Study:

  • To investigate the regulation of CD4 cell surface expression during T cell activation.
  • To determine the effect of glucocorticoids, specifically corticosterone (CORT), on CD4 expression and T cell proliferation.
  • To explore the functional significance of altered CD4 expression in T cell responses.

Main Methods:

  • T cell activation using plate-bound anti-TCR/anti-CD3 antibodies or soluble activators (staphylococcal enterotoxin A, Con A).
  • Quantification of CD4 cell surface expression on CD25+ cells via flow cytometry.
  • Assessment of T cell proliferation and sensitivity to anti-CD4 antibody inhibition.

Related Experiment Videos

  • Analysis of TCR down-regulation.
  • Main Results:

    • T cell activation led to a significant (up to 3-fold) increase in CD4 expression on CD25+ cells, peaking at 72-96 hours.
    • Corticosterone (CORT) treatment accelerated CD4 expression enhancement by approximately 24 hours.
    • CORT-treated T cells exhibited profoundly enhanced proliferation and reduced sensitivity to anti-CD4 antibody-mediated inhibition.
    • TCR down-regulation remained unaffected by CORT treatment.

    Conclusions:

    • TCR-mediated signals and glucocorticoids are key physiological regulators of CD4 expression.
    • Enhanced CD4 expression contributes to the increased proliferative response observed with CORT treatment.
    • Findings suggest implications for CD4+ T cell sensitivity to HIV infection, as viral entry efficacy correlates with surface CD4 levels.