Increase of intracellular calcium is the essential signal for the expression of CD40 ligand.
CD40 ligand (CD40L) is present on activated but not on resting T cells. In contrast to the activation markers CD25 and CD71, a strong CD40L expression could be induced by calcium ionophore alone but not by phorbol 12-myristate 13-acetate (PMA). Ionomycin induced a very early mRNA and protein surface expression of CD40L within the first 2 h, whereas CD25 and CD71 did not appear earlier than 6 h after stimulation. The mitogens phytohemagglutinin and concanavalin A induced little CD40L, but together with PMA, a markedly increased CD40L expression was observed. In T cells stimulated with immobilized anti-CD3, co-stimulation with anti-CD28 or PMA induced an earlier and higher maximal CD40L expression. CD40L expression of purified T cells was higher and more prolonged compared to that of T cells in unseparated peripheral blood mononuclear cells. We conclude that the expression of CD40L on T cells is profoundly different from other early activation markers with regard to signal requirements, kinetics and the role of accessory cells in the system.
Nüsslein
H G
HG
Institute of Clinical Immunology and Rheumatology, University of Erlangen-Nürnberg, Germany.
Frosch
K H
KH
Woith
W
W
Lane
P
P
Kalden
J R
JR
Manger
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D023201:CD40 Ligand; D002118:Calcium / Q000502:physiology*; D002469:Cell Separation; D016572:Cyclosporine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007424:Intracellular Fluid; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008934:Mitogens / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011990:Receptors, Transferrin; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; C068126:CD71 antigen; D007476:Ionophores; D008562:Membrane Glycoproteins; D008934:Mitogens; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D023201:CD40 Ligand; D004533:Egtazic Acid; D015759:Ionomycin; D016572:Cyclosporine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium