Human endothelial cell costimulation of T cell IFN-gamma production.
J Immunol
; 159(7): 3247-56, 1997 Oct 01.
Article
de En
| MEDLINE
| ID: mdl-9317123
ABSTRACT
In this report, we show that human endothelial cells (EC) provide costimulatory signals to mitogen-activated CD4+ T cells to augment IFN-gamma production. We also show that EC can enhance responsiveness of the T cells to IL-12. While IL-12 has no effect on IFN-gamma production by cultured CD4+ T cells in the absence of EC, addition of IL-12 to T cell-EC cocultures augments IFN-gamma production by as much as fivefold. Separation of T cells from EC by a semipermeable membrane inhibits the effect of EC and IL-12 on IFN-gamma production. Anti-LFA-3 Abs, in the absence or presence of IL-12, inhibit EC costimulation of IFN-gamma production by up to 50%, while Abs to intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), LFA-1, and very late antigen-4 (VLA-4) have relatively little effect. Pretreatment of T cells with conditioned medium from T cell-EC cocultures, or with IL-2 or IL-1 alpha similarly primes CD4+ T cells for the costimulatory effect of IL-12 on IFN-gamma production. EC costimulation of IFN-gamma production is inhibited by cyclosporine. However, in the presence of IL-12 there is a marked resistance to this inhibitory effect, suggesting that the IL-12-induced costimulatory pathway is distinct from the costimulatory pathway activated by endothelium alone. Our data are consistent with the hypothesis that, as a consequence of interactions with endothelium, T cells that migrate into an inflammatory site are primed to have enhanced responses to Ag and cytokine(s), such as IL-12, that influence T cell-cytokine production.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Endothélium vasculaire
/
Lymphocytes T CD4/
/
Interféron gamma
Limites:
Humans
Langue:
En
Journal:
J Immunol
Année:
1997
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique