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.