Endothelial cells augment the expression of CD40 ligand on newly activated human CD4+ T cells through a CD2/LFA-3 signaling pathway
✍ Scribed by Karin Karmann; Christopher C. W. Hughes; William C. Fanslow; Jordan S. Pober
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 821 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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 observable at 24 h. E C 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 are present. Blocking monoclonal antibodies to co-stimulatory molecules on E C 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 upregulation 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 E C provide unique co-stimulatory signals that affect the phenotype of activated CD4' T cells.