Article: article from journal or magazin.
Cyclosporin A inhibits CD40 ligand expression in T lymphocytes
Journal of Clinical Investigation
PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
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
Adolescent/Adult/CD40 Ligand/Calcineurin/Calmodulin-Binding Proteins/physiology/Child/Cyclosporine/pharmacology/Female/Humans/Immunoglobulin Class Switching/drug effects/Male/Membrane Glycoproteins/analysis/Phosphoprotein Phosphatase/Receptors,Interleukin-2/T-Lymphocytes/chemistry/Tetradecanoylphorbol Acetate/Research
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