Cyclosporin A inhibits CD40 ligand expression in T lymphocytes.

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  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Print ISSN: 0021-9738 (Print) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
    • Publication Information:
      Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
      Original Publication: New Haven [etc.] American Society for Clinical Investigation.
    • Subject Terms:
      Cyclosporine/*pharmacology ; Membrane Glycoproteins/*analysis ; T-Lymphocytes/*drug effects; Adolescent ; Adult ; CD40 Ligand ; Calcineurin ; Calmodulin-Binding Proteins/physiology ; Child ; Female ; Humans ; Immunoglobulin Class Switching/drug effects ; Male ; Phosphoprotein Phosphatases/physiology ; Receptors, Interleukin-2/analysis ; T-Lymphocytes/chemistry ; Tetradecanoylphorbol Acetate/pharmacology
    • 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.
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    • Grant Information:
      AI31136 United States AI NIAID NIH HHS; AI31541 United States AI NIAID NIH HHS; RR-02172 United States RR NCRR NIH HHS
    • Accession Number:
      0 (Calmodulin-Binding Proteins)
      0 (Membrane Glycoproteins)
      0 (Receptors, Interleukin-2)
      147205-72-9 (CD40 Ligand)
      83HN0GTJ6D (Cyclosporine)
      EC 3.1.3.16 (Calcineurin)
      EC 3.1.3.16 (Phosphoprotein Phosphatases)
      NI40JAQ945 (Tetradecanoylphorbol Acetate)
    • Publication Date:
      Date Created: 19940301 Date Completed: 19940421 Latest Revision: 20181113
    • Publication Date:
      20240829
    • Accession Number:
      PMC294093
    • Accession Number:
      10.1172/JCI117089
    • Accession Number:
      7907604