Endothelial cells augment the expression of CD40 ligand on newly activated human CD4+ T cells through a CD2/LFA-3 signaling pathway.
Cultured human endothelial cells (EC) increase CD40 ligand expression on polyclonally activated human peripheral blood CD4+ helper T cells compared to T cells activated in the absence of accessory cells or in the presence of peripheral blood adherent cells or B cells. Induction of CD40 ligand expression appears to be biphasic with early induction observable at 6 h and later induction at 24 h. EC cause T cells to increase CD40 ligand expression during the early phase at 6 h after activation. CD40 ligand expression is restricted to the CD4+ helper T cell subset of the peripheral blood T cells, even when EC is present. Blocking monoclonal antibodies to co-stimulatory molecules on EC and T cells indicate that the CD2/LFA-3 pathway, which also contributes to induction of augmented interleukin-2 (IL-2) secretion is involved in EC-induced up-regulation of CD40 ligand. Exogenous IL-2 can also increase CD40 ligand expression. However, increased IL-2 secretion in the presence of EC can not fully account for endothelial-induced CD40 ligand up-regulation as (1) the effect of exogenous IL-2 is greater at 24 h than at 6 h, whereas the opposite is true for EC; (2) the effect of saturating levels of IL-2 is considerably smaller than that of EC; and (3) blocking of IL-2 receptors does not fully inhibit endothelial effects on CD40 ligand expression. We conclude that EC provide unique co-stimulatory signals that effect the phenotype of activated CD4+ T cells.
Karmann
K
K
Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536-0812, USA.
Hughes
C C
CC
Fanslow
W C
WC
Pober
J S
JS
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand; D018968:CD58 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000097:blood; D010835:Phytohemagglutinins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018968:CD58 Antigens; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D023201:CD40 Ligand