Glucocorticoids inhibit CD40 ligand expression of peripheral CD4+ lymphocytes.
The ligand for CD40 (CD40L) is a type II transmembrane glycoprotein that 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 CD40. We show that dexamethasone in vitro inhibits CD40L expression in a dose-dependent manner in concentrations ranging from 0.1 to 1 mg/mL. Semiquantitative analysis of CD40L mRNA by RT-PCR revealed that this effect was due to inhibition of CD40L transcription. The inhibitory effect of dexamethasone 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 CD40L after incubation in medium alone for 48 h. Dexamethasone also inhibited PMA/ionomycin induced IL-2 and IFN-gamma production but not CD25 and CD69 expression. Glucocorticoids may exert their immunosuppressive effect in part by suppression of CD40L. Regulation of CD40L expression is steroid sensitive and may be similar or in part identical with IL-2 and IFN-gamma regulation.
Bischof
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F
Department of Neurology, Eberhardt Karls University, Tübingen, Germany. Felix.Bischof@uni-tuebingen.de
Melms
A
A
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D023201:CD40 Ligand; D017931:DNA Primers / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D023201:CD40 Ligand; D017931:DNA Primers; D003907:Dexamethasone; D005938:Glucocorticoids; D007371:Interferon-gamma; D007376:Interleukin-2; D015759:Ionomycin; D007476:Ionophores; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens