Esculetin inhibits T cell activation without suppressing IL-2 production or IL-2 receptor expression.
Esculetin (6,7-dihydroxycoumarin) was found to inhibit dose-dependently the proliferation of human T cells stimulated by PHA or phorbolester plus ionomycin. Proliferation in autologous and allogeneic MLR and generation of cytotoxic T cells under limiting dilution conditions were also suppressed, with more than 90% inhibition seen at 50 microM esculetin. The immunosuppressive effect of esculetin was not due to toxicity. Esculetin did not inhibit interleukin-2 (IL-2) production, nor did it interfere with the appearance of IL-2 receptors on stimulated T cells, as judged by immunofluorescence using anti-Tac monoclonal antibody. These results show that esculetin inhibits T-cell activation at a site distal to production of IL-2 and IL-2 receptor expression.
Kabelitz
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Department of Medical Microbiology, University of Ulm, F.R.G.
Al-Gorany
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KH
D000911:Antibodies, Monoclonal; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014468:Umbelliferones / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014468:Umbelliferones; C007628:esculetin