Cyclosporin A inhibits CD40 ligand expression in T lymphocytes

Ramsay Fuleihan*, Narayanaswamy Ramesh, Anthony Horner, Deborah Ahern, Peter J. Belshaw, David G. Alberg, Ivan Stamenkovic, William Harmon, Raif S. Geha

*Corresponding author for this work

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1315-1320
Number of pages6
JournalJournal of Clinical Investigation
Volume93
Issue number3
DOIs
StatePublished - Mar 1994

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Keywords

  • calcineurin
  • gene activation
  • immunosuppressants
  • transcription factors
  • transplantation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fuleihan, R., Ramesh, N., Horner, A., Ahern, D., Belshaw, P. J., Alberg, D. G., Stamenkovic, I., Harmon, W., & Geha, R. S. (1994). Cyclosporin A inhibits CD40 ligand expression in T lymphocytes. Journal of Clinical Investigation, 93(3), 1315-1320. https://doi.org/10.1172/JCI117089