Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells: evidence for posttranscriptional regulation

Transplantation. 1996 Oct 27;62(8):1113-8. doi: 10.1097/00007890-199610270-00016.


In T cells stimulated through the T cell receptor (TCR), both cyclosporine (CsA) and glucocorticoids (GC) inhibit the transcription of the IL-2 gene. In these cells costimulation via the CD28 cell surface molecule further increases the transcription of IL-2 and stabilizes its mRNA, resulting in a 20-30 fold induction in IL-2 production. This pathway is relatively resistant to the inhibitory effect of CsA. In this study, we asked whether GC interfere with CD28-mediated costimulatory signals for T cell activation. Primary human T cells or Jurkat T cells were stimulated with anti-CD28 and phorbol myristate acetate (PMA) in the presence of dexamethasone (Dex, 10(-10)-10(-5) M). Dex inhibited both the mRNA for IL-2 and IL-2 production in a dose-dependent fashion (minimum effective dose 10(-9) M). In similar experiments employing anti-CD3 mAb and PMA, a 7-20 fold higher concentration of Dex was required to obtain comparable inhibition. To determine if transcriptional modulation is occurring, Jurkat T cells were transfected with a plasmid containing the IL-2 promoter linked to the chloramphenicol acetyl transferase reporter gene. Following stimulation with ionomycin and PMA, high doses (10(-6) M) of Dex inhibited the activity of the IL-2 promoter (approximately 50% inhibition). However, in the presence of anti-CD28 mAb, this promoter became resistant to Dex (< or = 10% inhibition). These results suggest that GC inhibit accessory pathways for IL-2 production via CD28 by predominantly posttranscriptional mechanisms. Inhibition of the CD28 pathway may be an important mechanism for the T cell directed immunosuppressive effects of low-to-moderate doses of GC.

MeSH terms

  • Antibodies / drug effects
  • CD28 Antigens / immunology
  • CD28 Antigens / physiology*
  • CD3 Complex / immunology
  • Dexamethasone / pharmacology
  • Glucocorticoids / pharmacology*
  • Humans
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / genetics
  • Phorbol Esters / pharmacology
  • RNA Processing, Post-Transcriptional / physiology
  • RNA, Messenger / physiology
  • T-Lymphocytes / metabolism*
  • Transcription, Genetic / drug effects


  • Antibodies
  • CD28 Antigens
  • CD3 Complex
  • Glucocorticoids
  • Interleukin-2
  • Phorbol Esters
  • RNA, Messenger
  • Dexamethasone