Cyclosporin A inhibits CD40 ligand expression in T lymphocytes

J Clin Invest. 1994 Mar;93(3):1315-20. doi: 10.1172/JCI117089.


The ligand for CD40 is expressed on activated T lymphocytes and delivers contact-dependent activation signals to B lymphocytes. The mechanisms regulating CD40 ligand gene expression are largely unknown. Optimal expression of CD40 ligand required activation of protein kinase C and a rise in intracellular calcium concentration. CD40 ligand expression was inhibited by pretreatment of T cells with cyclosporin A. Cyclosporin A analogues inhibited CD40 ligand expression with a potency mirroring the ability of each compound to inhibit calcineurin activity, indicating that calcineurin plays a key role in CD40 ligand gene expression. Cyclosporin A inhibited IL-4-driven CD40 ligand-dependent IgE isotype switching in PBMC but did not inhibit IgE synthesis induced by CD40 mAb plus IL-4. PBMC derived from transplant patients receiving cyclosporin A failed to express CD40 ligand upon stimulation. These results suggest that patients receiving cyclosporin A may be deficient in CD40 ligand-dependent T cell help.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • CD40 Ligand
  • Calcineurin
  • Calmodulin-Binding Proteins / physiology
  • Child
  • Cyclosporine / pharmacology*
  • Female
  • Humans
  • Immunoglobulin Class Switching / drug effects
  • Male
  • Membrane Glycoproteins / analysis*
  • Phosphoprotein Phosphatases / physiology
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / drug effects*
  • Tetradecanoylphorbol Acetate / pharmacology


  • Calmodulin-Binding Proteins
  • Membrane Glycoproteins
  • Receptors, Interleukin-2
  • CD40 Ligand
  • Cyclosporine
  • Calcineurin
  • Phosphoprotein Phosphatases
  • Tetradecanoylphorbol Acetate