GLUCOCORTICOIDS INHIBIT CD40 LIGAND EXPRESSION OF PERIPHERAL CD4(+) LYMPHOCYTES

The ligand for CD40 (CD40L) is a type. II transmembrane glycoprotein t hat belongs to the tumor necrosis factor superfamily. CD40L expression on peripheral CD4(+) cells is increased upon activation and delivers signals to B lymphocytes which constitutively express CD PO. We show t hat dexamethasone in vitro inhibits CD40L expression in a dose-depende nt manner in concentrations ranging from 0.1 to 1 mg/mL. Semiquantitat ive analysis of CD40L mRNA by RT-PCR revealed that this effect was due to inhibition of CD40L transcription, The inhibitory effect of dexame thasone on CD40L expression was reversible and not due to affection of cell viability. Lymphocytes which have been exposed to dexamethasone in vitro retained the ability to express CD IOL after incubation in me dium alone for 48 h. Dexamethasone also inhibited PMA/ionomycin induce d IL-2 and IFN-gamma production but not CD25 and CD69 expression. Gluc ocorticoids may exert their immunosuppressive effect in part by suppre ssion of CD40L. Regulation of CD40L expression is steroid sensitive an d may be similar or in part identical with IL-2 and IFN-gamma regulati on. (C) 1998 Academic Press.